WEBVTT 00:00.000 --> 00:30.000 position:50% align:top line:0% *This machine-generated transcript may have errors. If remediation or a manually-generated transcript is needed, please contact NLM Support at https://support.nlm.nih.gov.* 00:01.430 --> 00:03.160 I'm Hansel Vigor 00:04.240 --> 00:06.900 pediatrician and geneticist from the 00:06.900 --> 00:09.850 University of Iowa Iowa City Iowa, 00:10.340 --> 00:13.150 I'm going to talk to you today about 00:13.160 --> 00:15.830 approaches to floppy babies 00:15.950 --> 00:18.700 and weak Children and genetic 00:18.700 --> 00:19.460 counseling. 00:20.540 --> 00:23.250 Floppy infant floppy penis 00:23.300 --> 00:25.510 is a rather new world 00:25.520 --> 00:27.460 creation which 00:27.470 --> 00:30.260 replaced the Previous term. 00:30.270 --> 00:32.550 A my zero Tony A congenital, 00:32.560 --> 00:33.030 am I? 00:33.030 --> 00:35.060 Oh Tony a congenital Oppenheim. 00:35.540 --> 00:38.450 Yet floppy penis is just 00:38.460 --> 00:40.960 as poorly delineated as 00:40.960 --> 00:43.610 poorly defined as a maya 00:43.610 --> 00:44.350 Tonia. 00:44.360 --> 00:47.140 Congenital was it has 00:47.140 --> 00:48.340 several meanings. 00:48.620 --> 00:50.620 It means week infant. 00:50.980 --> 00:53.450 It means high platonic infant 00:54.040 --> 00:56.800 or it means both weakness 00:56.810 --> 00:57.960 and hypo Tonia. 00:58.640 --> 01:00.860 There is no need for me to define 01:01.240 --> 01:03.350 for you muscular weakness. 01:03.660 --> 01:06.270 But what is the definition of hippo 01:06.270 --> 01:06.860 Tonia? 01:07.210 --> 01:09.400 This is shown in the first slide. 01:10.040 --> 01:12.570 Hippo Tonia is characterized by 01:12.580 --> 01:15.380 decreased re systems of the 01:15.380 --> 01:17.200 muscle to passive movements. 01:17.320 --> 01:18.880 And I mean, 01:18.890 --> 01:20.750 of the resting muscles. 01:21.340 --> 01:23.890 If a baby cries and as you know, 01:23.890 --> 01:26.310 a baby cries with all the four extremities, 01:26.320 --> 01:28.830 you would not be able 01:28.890 --> 01:31.150 to test the muscle tone, 01:31.640 --> 01:33.880 the baby has to be in the rest 01:33.890 --> 01:36.890 before you can measure the 01:36.900 --> 01:39.500 resistance of the muscle to passive 01:39.510 --> 01:40.160 movements, 01:40.540 --> 01:42.780 to softness of the muslim. 01:42.790 --> 01:44.240 If you pulpit the hype, 01:44.240 --> 01:45.350 a tonic muscle, 01:45.530 --> 01:48.390 it feels very soft and 01:48.400 --> 01:50.900 three hyper extensive 01:50.900 --> 01:52.260 bility of muslim. 01:52.740 --> 01:54.920 Now this is not always easily 01:54.920 --> 01:57.740 distinguishable from hyper lex 01:57.740 --> 01:59.550 city of the joints. 02:00.740 --> 02:02.680 Very often it is 02:02.810 --> 02:04.060 combined. 02:04.440 --> 02:07.230 That means the hyper extensively of 02:07.240 --> 02:09.600 muscle and hyper laxity of joints. 02:10.140 --> 02:10.510 Now, 02:10.510 --> 02:13.270 what are the manifestations of 02:13.270 --> 02:14.120 hyper Tony? 02:14.120 --> 02:17.090 Um we test hippo Tonia by 02:17.090 --> 02:19.020 the head drop phenomenon. 02:19.400 --> 02:21.760 The child 02:22.540 --> 02:24.850 raised inadvertently on 02:25.440 --> 02:26.850 his shoulders. 02:27.340 --> 02:28.770 In high platonic Children, 02:28.770 --> 02:30.800 the head drops back clearly. 02:30.810 --> 02:33.540 You can only make this test the head drop 02:33.540 --> 02:36.060 phenomenon after head control has been 02:36.070 --> 02:36.640 achieved. 02:36.650 --> 02:37.190 That means, 02:37.200 --> 02:39.640 after the first year of 02:39.640 --> 02:40.280 life, 02:40.290 --> 02:41.230 the frog belly. 02:41.240 --> 02:44.120 If the child is lying on his 02:44.120 --> 02:44.770 back, 02:44.780 --> 02:47.780 the abdomen extends 02:47.790 --> 02:50.600 laterally over the two oracle wall. 02:50.610 --> 02:52.200 The scar phenomenon, 02:52.210 --> 02:55.200 If you bring the arm around the 02:55.200 --> 02:56.570 neck of the child, 02:56.580 --> 02:59.310 the shoulder will come under the chin 02:59.320 --> 03:02.090 or even on the other side of the 03:02.090 --> 03:02.390 index. 03:02.390 --> 03:04.780 The scar phenomenon lose shoulders, 03:04.790 --> 03:06.970 rectal phenomenon gina, 03:06.970 --> 03:09.170 record bottom etcetera. 03:09.180 --> 03:10.860 These are some of the 03:10.870 --> 03:13.870 manifestations by which 03:13.880 --> 03:15.960 we can test hyper Tonia. 03:17.040 --> 03:17.340 Now, 03:17.340 --> 03:18.630 if I say it before, 03:18.640 --> 03:21.560 that floppy penis can mean different 03:21.560 --> 03:23.680 things has different meanings. 03:24.840 --> 03:26.890 There are two major 03:26.890 --> 03:29.780 category of hyper 03:29.780 --> 03:30.290 Tonia, 03:30.300 --> 03:33.220 namely cerebral hippo 03:33.220 --> 03:33.880 Tonia, 03:33.890 --> 03:36.190 also called super 03:36.190 --> 03:38.960 spinal hyper 03:38.960 --> 03:39.720 Tonia. 03:39.730 --> 03:41.870 Non paralytic hyper Tonia, 03:41.880 --> 03:42.930 super nuclear, 03:42.930 --> 03:43.760 high petunia. 03:44.140 --> 03:46.020 Here we have HIPPA Tonia, 03:46.030 --> 03:48.330 but very often there is a discrepancy 03:48.330 --> 03:51.070 between decreased tone and 03:51.070 --> 03:52.550 fairly good muscle strength. 03:52.560 --> 03:55.540 That means if you have a high platonic child 03:55.550 --> 03:57.160 in rest who, 03:57.170 --> 03:59.820 when crying and struggling has pretty good 03:59.830 --> 04:01.660 resistance in his muscles, 04:01.840 --> 04:04.740 you are likely to assume that this is a 04:04.740 --> 04:07.340 cerebral or super 04:07.350 --> 04:09.420 nuclear high petunia. 04:09.430 --> 04:11.990 The reflexes in cerebral dependent 04:11.990 --> 04:14.810 reflexes that is in super nuclear 04:14.810 --> 04:15.270 hype. 04:15.270 --> 04:18.140 A Tonia are positive, 04:18.150 --> 04:20.620 active hyperactive or even 04:20.630 --> 04:23.130 exaggerated CPK for 04:23.130 --> 04:25.230 creating forceful kindness E. 04:25.230 --> 04:25.430 M. 04:25.430 --> 04:25.880 G. 04:25.890 --> 04:27.360 For electro biography. 04:27.540 --> 04:30.360 Our normal muscle biopsy is normal. 04:31.540 --> 04:32.380 On the other hand, 04:32.380 --> 04:35.160 there is a paralytic form of high petunia 04:35.540 --> 04:38.120 and a distal peripheral form 04:38.130 --> 04:38.860 here. 04:38.870 --> 04:41.290 HIPPA Tonia and weakness go 04:41.290 --> 04:42.100 parallel. 04:42.110 --> 04:44.690 You have muscle weakness and at the same 04:44.690 --> 04:45.130 time, 04:45.140 --> 04:46.760 muscular hypothermia. 04:47.200 --> 04:49.700 The reflexes may be decreased or 04:49.710 --> 04:50.350 absent. 04:50.940 --> 04:53.460 CPK creating false for kindness, 04:53.470 --> 04:55.230 may be high or normal. 04:55.240 --> 04:55.870 E. 04:55.870 --> 04:56.090 M. 04:56.090 --> 04:56.490 G. 04:56.500 --> 04:59.270 Is abnormal and the muscle biopsy is 04:59.280 --> 05:00.260 abnormal. 05:02.240 --> 05:02.960 No, 05:04.340 --> 05:06.730 I'm not going to talk to you 05:06.740 --> 05:09.470 about the paralytic form of hypo 05:09.470 --> 05:12.450 Tony because this has been discussed by other speakers 05:12.450 --> 05:13.420 before me, 05:13.430 --> 05:16.220 but any lesion in the 05:16.220 --> 05:17.560 peripheral reflects it, 05:17.570 --> 05:18.140 be it, 05:18.140 --> 05:20.370 the different gamma aphorisms, 05:20.490 --> 05:21.930 the anterior horn cells, 05:21.930 --> 05:23.700 spinal muscular atrophy, 05:23.710 --> 05:26.160 the peripheral neurons, 05:26.170 --> 05:28.000 Charcot Marie tooth disease. 05:28.010 --> 05:29.910 The neuromuscular synapses. 05:29.910 --> 05:30.610 Myasthenia, 05:30.610 --> 05:31.090 gravis, 05:31.100 --> 05:33.890 or the muscle for myopathy may 05:33.890 --> 05:36.890 be affected uh in this 05:36.900 --> 05:39.470 uh paralytic 05:39.480 --> 05:40.960 form of hyper Tony. 05:40.960 --> 05:41.940 Um as I say, 05:41.940 --> 05:44.030 I'm not going to talk about this. 05:44.040 --> 05:46.910 I would like to talk about 05:46.920 --> 05:49.690 some of the super nuclear 05:49.700 --> 05:52.470 or non paralytic 05:52.480 --> 05:53.960 hyper Tonia. 05:54.140 --> 05:56.560 Let us remember that 05:57.140 --> 05:59.740 any cerebral palsy or 05:59.750 --> 06:01.490 non progressive 06:01.500 --> 06:03.710 encephalopathy is 06:03.720 --> 06:06.560 hypo tonic in early 06:06.570 --> 06:09.340 infancy take an extra peter middle 06:09.500 --> 06:11.350 form of several policy. 06:11.940 --> 06:14.450 The child may be hyper tonic, 06:14.460 --> 06:17.420 but the extra pyramidal hyper kinesis 06:17.430 --> 06:20.350 cannot be distinguished from the 06:20.350 --> 06:23.200 physiological mass movements in early 06:23.210 --> 06:23.910 infancy. 06:23.920 --> 06:25.920 And it takes off often 06:25.930 --> 06:28.900 656 months until 06:28.900 --> 06:31.440 we can finally distinguish that, 06:31.440 --> 06:31.980 for instance. 06:31.990 --> 06:33.560 Important in currently truth, 06:33.840 --> 06:36.240 there's a child with actress. 06:36.240 --> 06:39.240 Kravis has developed connectors are not often. 06:39.250 --> 06:41.740 It takes 56 months until we are 06:41.750 --> 06:43.880 able to make the distinction 06:43.890 --> 06:46.770 because of this physiologic 06:46.780 --> 06:47.940 mass movement. 06:47.950 --> 06:49.760 In the first few months of life, 06:50.440 --> 06:52.490 the cerebellum form of 06:52.500 --> 06:55.040 uh cerebral policy. 06:55.050 --> 06:55.600 Well, 06:55.610 --> 06:58.350 it takes about the year before a child becomes 06:58.350 --> 07:00.870 tactic before a child develops balance. 07:00.880 --> 07:03.270 Therefore the ataxia and the 07:03.270 --> 07:06.120 disturbance of balance cannot be 07:06.120 --> 07:09.100 recognized before a child is at least 07:09.100 --> 07:11.570 one year old and therefore we 07:11.570 --> 07:14.570 can we cannot make a diagnosis of 07:14.570 --> 07:16.770 cerebral cerebellum 07:17.240 --> 07:20.220 uh cerebral policy before 07:20.230 --> 07:21.530 the age of one year. 07:21.540 --> 07:23.120 But even the Kartik, 07:23.120 --> 07:25.830 the cortical lesions remember that 07:25.840 --> 07:27.800 any spastic of not any, 07:27.800 --> 07:30.800 but almost any uh 07:30.810 --> 07:33.800 spastic cerebral policy is in the 07:33.800 --> 07:36.160 beginning hype a tonic. 07:36.340 --> 07:37.920 It takes weeks, 07:37.930 --> 07:40.330 months or even years 07:40.340 --> 07:42.680 until spasticity they appeared. 07:42.690 --> 07:45.620 And in some cases spasticity 07:45.620 --> 07:46.760 never occurs. 07:46.770 --> 07:49.230 They remain high platonic 07:49.240 --> 07:50.940 or a tonic. 07:50.950 --> 07:53.570 We have a generalized catatonia with 07:53.570 --> 07:54.650 soft muscle, 07:54.660 --> 07:56.760 the tendon reflexes maybe 07:57.040 --> 07:59.450 elicited or even be exaggerated. 07:59.450 --> 08:02.450 You may have an extensive planet response and the 08:02.450 --> 08:05.210 psycho motor development may or 08:05.210 --> 08:06.930 may not be delayed. 08:06.940 --> 08:09.890 That is the so called a tonic die, 08:09.890 --> 08:10.320 please. 08:10.940 --> 08:13.930 Which in milder form is not easily 08:13.930 --> 08:16.580 distinguished from the so called essential 08:16.590 --> 08:18.270 hypo Tony. 08:18.270 --> 08:20.850 Um No. 08:22.140 --> 08:24.650 Let's make a few words 08:24.660 --> 08:26.080 about, 08:26.090 --> 08:29.030 say a few words about the benign 08:29.030 --> 08:31.430 congenital or essential 08:31.430 --> 08:32.550 hypothermia. 08:32.560 --> 08:35.430 Usually I discuss this 08:35.440 --> 08:37.850 at the end because this is really a 08:37.850 --> 08:40.100 diagnosis of exclusion. 08:40.340 --> 08:43.160 But for the flow of this present discussion, 08:43.240 --> 08:45.810 I bring the 08:45.820 --> 08:48.770 essential high petunia at this 08:48.770 --> 08:50.760 point and we'll discuss it now. 08:50.760 --> 08:53.260 How are these Children come to you? 08:53.270 --> 08:55.690 They are sent to you with the following 08:55.690 --> 08:58.450 complaints is emphatic ability 08:58.740 --> 09:01.200 or the child shows frequent fallings. 09:01.200 --> 09:02.460 It has big legs, 09:02.460 --> 09:03.860 it had loose joints, 09:04.040 --> 09:06.530 it has a crooked gate. 09:06.540 --> 09:09.000 There is some delay in motor development. 09:09.010 --> 09:11.990 These are the complaints the parents expressed to 09:11.990 --> 09:12.350 you. 09:12.740 --> 09:15.180 The doctors may send you the child under the 09:15.180 --> 09:15.890 diagnosis, 09:15.900 --> 09:18.260 A maya Tonia or even muscular 09:18.260 --> 09:19.060 dystrophy. 09:19.070 --> 09:20.270 Down syndrome, 09:20.280 --> 09:21.010 et cetera. 09:21.020 --> 09:22.510 What are the 09:22.510 --> 09:24.400 manifestations of 09:24.410 --> 09:25.690 benign, 09:25.700 --> 09:28.570 congenital or essential hype? 09:28.570 --> 09:29.360 A Tonia? 09:30.040 --> 09:31.560 There is hipAA Tonia. 09:31.570 --> 09:34.150 As we have seen in one of the previous lights. 09:34.160 --> 09:36.930 The tendon reflexes are normal or 09:36.930 --> 09:37.860 depressed. 09:37.870 --> 09:39.000 They are Pandelis. 09:39.000 --> 09:41.170 That means if you check 09:41.170 --> 09:43.770 your knee jerk, 09:43.780 --> 09:46.520 you will see that after you get the reflects it 09:46.550 --> 09:49.240 handles uh back and forth for a while. 09:49.250 --> 09:51.840 Due to the to the decrease gamma 09:51.850 --> 09:52.700 responses. 09:52.950 --> 09:55.650 There is often hyperlink city of the joints. 09:56.040 --> 09:59.020 Some strength is okay with the child struggles. 09:59.030 --> 10:00.390 It has pretty good strength. 10:00.400 --> 10:02.470 Sometimes could dislikes term. 10:02.470 --> 10:04.760 Oh and like liability. 10:05.440 --> 10:06.840 Now the E. 10:06.840 --> 10:07.050 M. 10:07.050 --> 10:07.420 G. 10:07.430 --> 10:08.460 Is normal. 10:08.500 --> 10:11.160 The motor nerve conduction velocity is normal. 10:11.170 --> 10:13.830 Creatine kindness is normal. 10:13.840 --> 10:15.420 Muscle biopsy is normal. 10:15.420 --> 10:17.760 Sometimes you find small muscle 10:17.760 --> 10:20.450 fibers and course in Belgium 10:20.450 --> 10:22.900 some years ago has shown that there is a 10:22.910 --> 10:25.650 defective arab authorization of the 10:25.660 --> 10:28.270 intra muscular nerve endings. 10:28.280 --> 10:29.390 The genetics, 10:29.400 --> 10:31.540 many cases are sporadic. 10:31.550 --> 10:32.880 Others are familiar. 10:32.890 --> 10:35.640 Even families with autism, 10:35.640 --> 10:35.860 alert, 10:35.860 --> 10:38.550 dominant inheritance of this condition 10:38.640 --> 10:39.860 has been reported. 10:40.340 --> 10:42.900 The prognosis is usually good. 10:44.140 --> 10:45.630 If I see a child, 10:45.840 --> 10:48.500 I have the feeling that is an 10:48.510 --> 10:51.350 essential benign congenital hypo 10:51.350 --> 10:52.040 Tonia, 10:52.050 --> 10:54.300 I tell the parents well let's wait, 10:54.300 --> 10:57.060 let's see if my diagnosis correct, 10:57.440 --> 10:59.530 then The hyper Tony will 10:59.540 --> 11:02.120 disappear by the age at least 11:02.170 --> 11:03.650 10 years at the latest. 11:04.140 --> 11:06.960 But If by 10 years the di 11:06.970 --> 11:09.330 the opportunity is still present. 11:09.340 --> 11:12.140 Then you have to think of various condition as 11:12.140 --> 11:15.080 mentioned here and also of some of 11:15.090 --> 11:17.650 the benign congenital myopathy. 11:18.240 --> 11:21.020 Now just recently we had a five years 11:21.020 --> 11:23.940 old boy who came and 11:23.950 --> 11:26.410 we felt that this could be an essential 11:26.410 --> 11:27.270 hypothermia. 11:27.280 --> 11:28.250 However, 11:28.260 --> 11:30.950 the boy had a tendency to walk on his 11:30.950 --> 11:31.640 tiptoes. 11:31.680 --> 11:34.640 There was already slight achillestendon contractor which 11:34.640 --> 11:36.790 was a little bit more than essential 11:36.790 --> 11:37.650 hypothermia. 11:37.940 --> 11:40.460 Now we decided uh the 11:40.470 --> 11:43.170 orthopedic surgeon decided to do a tendon lengthening 11:43.170 --> 11:46.010 operation and we decided to study the most 11:46.020 --> 11:46.670 muscle. 11:46.680 --> 11:49.680 And lo and behold what you see here 11:49.690 --> 11:52.270 is really a type 11:52.280 --> 11:53.830 two fiber positive. 11:53.830 --> 11:55.640 The dark fibers that's 80 P. 11:55.640 --> 11:56.410 A steam. 11:56.420 --> 11:58.970 The dark fibers are Type two fibers. 11:58.980 --> 12:01.640 The clear fibers are The type one 12:01.640 --> 12:02.140 fibers. 12:02.150 --> 12:05.080 There is a definite Type one Fiber 12:05.080 --> 12:07.900 predominance continue to fiber type 12:07.900 --> 12:10.840 disproportion or a positive of Type 12:10.850 --> 12:11.580 two fibers. 12:11.590 --> 12:14.460 You remember that this morning dr Engel was 12:14.460 --> 12:15.760 mentioning um 12:16.640 --> 12:19.360 the positivity of Type two 12:19.360 --> 12:21.770 fibers as one possible 12:21.770 --> 12:24.340 cause of the 12:24.350 --> 12:26.140 essential hypothermia. 12:26.150 --> 12:28.580 We really don't know what essential hypertension. 12:28.580 --> 12:30.860 It it may be a 12:30.870 --> 12:33.460 multitude of conditions. 12:34.740 --> 12:37.290 But let's keep in mind that a congenital 12:37.290 --> 12:38.330 myopathy, 12:38.340 --> 12:41.180 a so called benign congenital myopathy 12:41.190 --> 12:43.580 may present under the 12:43.580 --> 12:44.850 clinical picture, 12:44.850 --> 12:47.050 may present the features of 12:47.060 --> 12:49.560 essential hypothermia. 12:50.540 --> 12:53.290 Now let's make a let's look at another slide. 12:53.300 --> 12:54.850 This girl here, 12:54.860 --> 12:57.640 I saw her for the first 12:57.650 --> 13:00.180 time at the age of about 10 13:00.190 --> 13:03.140 months at that time she was definitely 13:03.140 --> 13:04.060 high platonic, 13:04.440 --> 13:07.410 she was somebody late in motor development 13:07.410 --> 13:10.100 which I thought might be due to her 13:10.100 --> 13:11.090 hypothermia. 13:11.740 --> 13:13.900 I saw her again at 3.5 years. 13:13.910 --> 13:14.640 He or she is. 13:14.640 --> 13:17.290 She's still hippo Tony as you can see from this 13:17.290 --> 13:18.380 curb back. 13:18.380 --> 13:21.170 That's a sign of hypothermia at 13:21.180 --> 13:21.880 this time. 13:21.900 --> 13:24.460 She was definitely mentally retarded. 13:24.840 --> 13:27.290 Let's remember that mental 13:27.290 --> 13:29.800 retardation in the first year of 13:29.800 --> 13:32.270 life may present as hipaa 13:32.270 --> 13:32.920 Tonia. 13:32.930 --> 13:35.490 And you have to watch your child very 13:35.490 --> 13:38.230 carefully compare motor 13:38.240 --> 13:41.060 delay in motor development versus 13:41.070 --> 13:43.020 intellectual alertness. 13:43.030 --> 13:45.360 To make the differential diagnosis. 13:46.040 --> 13:46.610 Remember, 13:46.610 --> 13:47.130 for instance, 13:47.130 --> 13:48.940 the cases of Whitney Kaufman's disease, 13:48.950 --> 13:51.260 which may be completely paralyzed. 13:51.270 --> 13:53.840 But you remember that a lord 13:53.840 --> 13:54.280 looked. 13:54.280 --> 13:55.850 These Children have to do. 13:55.860 --> 13:58.780 That's a typical distinction 13:58.790 --> 14:01.630 between mental alertness and 14:01.640 --> 14:03.070 muscular hypothermia. 14:03.080 --> 14:05.730 Watch for your mentally retarded Children. 14:05.730 --> 14:06.600 Be careful, 14:06.600 --> 14:09.430 leave a little door opened when you talk to the 14:09.430 --> 14:09.920 parents. 14:10.340 --> 14:10.700 We, 14:10.710 --> 14:11.240 by the way, 14:11.240 --> 14:13.780 my students are never allowed to make a diagnosis. 14:13.780 --> 14:16.520 Mental retardation before a child is three years old 14:16.530 --> 14:19.530 because you may be mistaken on the other side 14:19.530 --> 14:19.980 as well. 14:20.090 --> 14:21.860 But keep this in mind. 14:23.940 --> 14:24.450 No, 14:25.140 --> 14:28.020 if I mentioned before in the slides 14:28.020 --> 14:30.470 where I talked about cerebral hypo 14:30.470 --> 14:31.740 Tonia, 14:31.750 --> 14:34.540 that there are preserved reflexes and 14:34.550 --> 14:36.860 there is a discrepancy between 14:37.740 --> 14:40.530 decreased muscle tone and 14:40.530 --> 14:41.910 good muscle strength. 14:41.920 --> 14:44.460 There are some exceptions to the rules. 14:45.040 --> 14:47.780 These exceptions are one the 14:47.780 --> 14:50.730 cerebrally depressed newborn depressed 14:50.740 --> 14:52.680 because of prenatal disease. 14:52.690 --> 14:54.800 Because of perinatal trauma, 14:54.800 --> 14:56.580 autism disease et cetera. 14:56.590 --> 14:58.660 I'm not going to talk about that. 14:59.240 --> 15:02.210 The cerebral hippo to renal 15:02.220 --> 15:02.900 syndrome, 15:02.910 --> 15:04.850 or Zellweger syndrome, 15:05.440 --> 15:08.300 shows severe catatonia, 15:08.310 --> 15:11.140 which you see here two Children with cerebral 15:11.140 --> 15:13.860 syndrome and you see this enormous hi 15:13.860 --> 15:14.740 Patagonia, 15:14.770 --> 15:17.720 this Daytona of the so called 15:17.730 --> 15:20.680 cerebro hepatic or renal or hepatic renal 15:20.680 --> 15:21.760 cerebral syndrome. 15:21.770 --> 15:24.640 Zellweger syndrome the 15:24.650 --> 15:26.850 the symptoms in brief our 15:26.860 --> 15:29.410 Daytona a reflexive but hip 15:29.410 --> 15:32.060 atomically with a tendency to victories in the 15:32.060 --> 15:34.710 second month Molina due to hyper 15:34.720 --> 15:36.590 pro trump anemia. 15:36.600 --> 15:39.020 No psycho motor development at all. 15:39.030 --> 15:41.750 Many Children have glaucoma cataract. 15:41.840 --> 15:44.090 Others have congenital 15:44.640 --> 15:47.360 um convulsions or a medium 15:47.360 --> 15:47.780 cortes. 15:47.780 --> 15:50.640 Congenital stippled epiphanies are quite 15:50.640 --> 15:51.210 frequent. 15:51.220 --> 15:53.870 I'm not going to talk about this syndrome is very 15:53.880 --> 15:56.710 much more because most of these 15:56.710 --> 15:59.330 Children die with him the first 15:59.330 --> 16:02.320 few months of life I 16:02.320 --> 16:03.410 would like however, 16:03.410 --> 16:06.120 to talk about two other exceptions to the 16:06.120 --> 16:08.510 rule where you have severe 16:08.520 --> 16:11.340 neonatal and infantile hypo 16:11.340 --> 16:12.010 Tonia, 16:12.020 --> 16:14.980 namely the Prader Willi syndrome and the 16:14.990 --> 16:17.930 early onset Maya Tonia tropical 16:17.940 --> 16:19.460 or Maya tonic dystrophy. 16:20.240 --> 16:20.780 First, 16:20.780 --> 16:21.870 Prader Willi syndrome. 16:22.440 --> 16:23.920 The Prader Willi syndrome, 16:23.930 --> 16:26.580 also called hype A Tonia. 16:26.590 --> 16:28.190 Hyper MENSA 16:28.200 --> 16:30.570 hypogonadism Obesity 16:30.570 --> 16:33.420 syndrome has two faces, 16:33.430 --> 16:36.390 namely a first phase in 16:36.400 --> 16:37.430 the newborn. 16:37.440 --> 16:40.440 In the first few months of life where the child is 16:40.450 --> 16:43.420 extremely a tonic reflexes, 16:43.580 --> 16:46.170 there is no sucking reflects no 16:46.170 --> 16:47.390 swelling or flex. 16:47.400 --> 16:49.740 I had Children whom I had to feed 16:49.750 --> 16:52.220 by nasal gastric tube for 16:52.220 --> 16:54.660 several months before they picked up. 16:54.840 --> 16:57.400 There's also deficient term regulation. 16:57.400 --> 16:58.270 There is small, 16:58.280 --> 17:00.730 a small hand and small feet. 17:00.740 --> 17:03.430 And the diagnosis in this early 17:03.440 --> 17:06.290 phase is very difficult, 17:06.300 --> 17:08.400 particularly girls in boys, 17:08.410 --> 17:11.250 it is somewhat easier because boys 17:11.260 --> 17:13.860 have an undescended testicle 17:13.940 --> 17:16.680 and they have behind the mini peanuts. 17:16.940 --> 17:19.670 Only a very 17:19.680 --> 17:22.620 hyper plastics growth not more than a 17:22.620 --> 17:24.630 little bit corrugated skin. 17:24.640 --> 17:27.520 If you have this with the symptoms shown 17:27.530 --> 17:28.720 in the previous slide, 17:28.730 --> 17:30.930 then you may be pretty 17:30.940 --> 17:33.310 sure that this is a 17:33.570 --> 17:34.780 village in girls. 17:34.790 --> 17:37.660 You have to wait until we enter the second 17:37.660 --> 17:38.270 phase, 17:38.640 --> 17:39.180 namely, 17:39.180 --> 17:40.500 after some months, 17:40.760 --> 17:42.130 these Children wake up, 17:42.140 --> 17:43.510 become more alert. 17:43.520 --> 17:45.170 They still are hyper tonic, 17:45.740 --> 17:48.180 but then they develop a peculiar 17:48.180 --> 17:49.570 hyper feature. 17:49.580 --> 17:51.590 They eat and eat and eat and eat. 17:51.600 --> 17:54.080 Some of them have a painful hunger 17:54.080 --> 17:56.960 feeling which takes them constantly 17:57.440 --> 17:59.630 and they have to eat constantly. 17:59.640 --> 18:01.760 They pill for the the the the 18:01.770 --> 18:04.590 the garbage can they eat 18:04.590 --> 18:06.220 the food of the dock? 18:06.230 --> 18:09.230 Because if if no food for them is 18:09.230 --> 18:09.900 available. 18:09.910 --> 18:10.740 Others, 18:10.750 --> 18:12.550 there may be two types of prey. 18:12.550 --> 18:15.440 The really others they eat only if food 18:15.450 --> 18:17.270 is before them and if it is taken, 18:17.540 --> 18:18.770 I really don't eat, 18:19.540 --> 18:22.310 but consequently they increase 18:22.320 --> 18:22.960 invade. 18:22.970 --> 18:25.740 They are mentally retarded and have a slurred 18:25.750 --> 18:26.560 speech. 18:27.240 --> 18:27.770 Now, 18:29.940 --> 18:32.940 in consequence to this uh to this 18:32.950 --> 18:34.940 hyper feature, 18:34.940 --> 18:37.340 to this enormous eating, 18:37.350 --> 18:38.730 the weight increases. 18:38.730 --> 18:41.250 See here this is the median line 18:41.250 --> 18:41.750 here. 18:41.760 --> 18:44.580 These are always curve here here and here and you 18:44.580 --> 18:47.530 see how in the later month of 18:47.540 --> 18:50.530 the first year the weight goes up in mind while 18:50.530 --> 18:53.200 the height remains in all Cases 18:53.210 --> 18:55.960 below the 50 time. 18:56.640 --> 18:59.480 Consequently these Children develop an 18:59.490 --> 19:02.070 enormous obesity. 19:02.080 --> 19:04.820 This is even a rather benign cases. 19:04.830 --> 19:07.160 We have seen much more 19:07.170 --> 19:08.670 severe obesity. 19:09.040 --> 19:10.360 What can we do for it? 19:10.370 --> 19:12.900 That is not within the the discussion 19:12.900 --> 19:13.470 today. 19:13.480 --> 19:16.220 But let me just say that we have in 19:16.220 --> 19:18.860 some cases done a gastric 19:18.860 --> 19:21.670 bypass operation in that the product 19:22.240 --> 19:24.540 the proximal part of the 19:24.550 --> 19:27.090 stomach is futures to the to 19:27.090 --> 19:29.900 the last part of the duodenum. 19:29.910 --> 19:32.510 More recently we have started to make a 19:32.510 --> 19:35.390 narrowing operation of the of the 19:35.400 --> 19:37.310 stomach as you see here. 19:37.320 --> 19:40.000 So the child can only eat until this part is 19:40.000 --> 19:40.380 full. 19:40.390 --> 19:43.160 And if this is full then he has to bomb attack like the 19:43.170 --> 19:44.250 old roman state. 19:44.260 --> 19:46.730 Only the did the vomiting not by 19:46.740 --> 19:49.150 a gastric narrowing operation but 19:49.160 --> 19:52.140 by uh teaching their their 19:52.140 --> 19:54.750 throat with a 19:54.760 --> 19:55.270 feather. 19:55.740 --> 19:58.620 But in principle that's not a very humane treatment. 19:58.630 --> 20:01.170 That's the only treatment we have to 20:01.180 --> 20:03.530 offer as to muscle. 20:03.710 --> 20:05.860 Sometimes you find a type 20:06.640 --> 20:09.080 two fiber atrophy probably due 20:09.080 --> 20:11.340 to atrophy due to disuse. 20:11.350 --> 20:14.120 And here you see an electron microgram of a 20:14.120 --> 20:16.890 Prader Willi here you see rather 20:16.890 --> 20:19.330 normal Miomir normal maya. 20:19.410 --> 20:21.870 But here you see a tremendous disarray. 20:21.870 --> 20:23.810 Still some muscle fibers around, 20:23.810 --> 20:26.670 but a lot of debris in between. 20:26.830 --> 20:29.810 That's the muscle in villy breeder 20:29.820 --> 20:30.450 syndrome. 20:32.440 --> 20:34.450 Now let's go to something else. 20:35.350 --> 20:37.740 This little boy I saw about 20:37.750 --> 20:39.660 20 years ago. 20:40.140 --> 20:42.430 He was severely hyper 20:42.430 --> 20:43.260 tonic. 20:43.840 --> 20:46.150 He had a delayed motor 20:46.150 --> 20:48.320 development at this when he was here. 20:48.320 --> 20:50.580 He was about 1 1/2 years old. 20:50.590 --> 20:53.400 His mother indicated that the feeding during the 20:53.400 --> 20:55.300 first few months of life had been 20:55.310 --> 20:57.420 extremely difficult, 20:57.430 --> 21:00.010 but she did not have to resort to nasal 21:00.020 --> 21:01.270 gastric feeding. 21:01.840 --> 21:03.730 I examined this child, 21:03.740 --> 21:06.100 the neurologist examined the child. 21:06.110 --> 21:08.060 Orthopedist examined the child. 21:08.070 --> 21:09.850 We couldn't come up with a clear cut, 21:09.850 --> 21:10.380 diagnosed, 21:10.380 --> 21:11.890 there was severe hyper Tony, 21:11.890 --> 21:14.740 you see a flat faced with a little bit triangle 21:14.750 --> 21:17.400 or shark mouth indicating official 21:17.400 --> 21:18.020 depleted. 21:18.210 --> 21:20.260 The reflexes were obtainable. 21:20.540 --> 21:23.370 We saw some special form of cerebral policy but 21:23.380 --> 21:23.970 we really, 21:23.980 --> 21:24.950 we were not sure. 21:25.640 --> 21:27.670 Well I lost sight of the child. 21:28.240 --> 21:30.360 Few years later I found him 21:30.940 --> 21:33.550 with his mother in the department of neurology. 21:33.940 --> 21:36.410 He had now typical 21:36.410 --> 21:39.380 signs of maya tonic dystrophy. 21:39.460 --> 21:41.210 The lady contractual 21:42.040 --> 21:42.870 percussion, 21:42.870 --> 21:43.650 my antonia. 21:43.660 --> 21:45.900 His mother has a monotonic dystrophy. 21:45.910 --> 21:48.800 His sister has my autonomic dystrophy 21:48.800 --> 21:49.270 as well. 21:49.840 --> 21:52.000 The boy is now 20 years old. 21:52.010 --> 21:54.410 You see here this typical swan 21:54.410 --> 21:57.240 leg of the maya tonic dystrophy. 21:57.250 --> 21:59.150 You see the flat face. 21:59.150 --> 22:01.720 You see he has a facial diaper teacher, 22:01.730 --> 22:02.730 he has, 22:02.740 --> 22:05.600 his speech is hardly 22:05.610 --> 22:06.420 understandable. 22:06.430 --> 22:09.310 Even his mother has difficulties to understand 22:09.310 --> 22:12.290 him and he is mentally retarded and still 22:12.300 --> 22:15.120 has typical signs of maya tonic 22:15.130 --> 22:18.100 dystrophy at the time when I saw this 22:18.100 --> 22:19.790 baby for the first time, 22:19.920 --> 22:22.270 I didn't know what it was and nobody news 22:22.560 --> 22:25.480 since then we know better because 22:25.490 --> 22:28.380 this condition has since then been 22:28.380 --> 22:29.950 described as 22:30.840 --> 22:33.380 congenital facial depledge A by parker. 22:33.380 --> 22:36.190 In 1963 BRzezinski gave it the 22:36.190 --> 22:37.340 name Maya tonic. 22:37.350 --> 22:40.080 This embryo play asia waters. 22:40.090 --> 22:43.070 We speak of early onset diatonic 22:43.070 --> 22:43.970 dystrophy, 22:43.980 --> 22:46.060 my atomic district in the neonatal 22:46.070 --> 22:48.580 congenital Destro fia maionica. 22:48.590 --> 22:51.350 These are all synonyms for 22:51.540 --> 22:51.860 it. 22:51.870 --> 22:52.350 Come 22:55.640 --> 22:58.600 for a condition which is 22:58.600 --> 23:00.170 characterized by 23:00.740 --> 23:02.860 decreased fetal movements. 23:03.440 --> 23:06.390 These mothers indicate that they have much 23:06.390 --> 23:09.020 less fetal movement than they had with other babies. 23:09.030 --> 23:11.390 Often there is hydrangeas 23:12.140 --> 23:14.770 in emphysema severe plutonium 23:14.960 --> 23:17.330 reflexes may be absent or 23:17.340 --> 23:18.170 decreased. 23:18.640 --> 23:21.400 The sucking reflects the swallowing reflex is 23:21.400 --> 23:24.240 decreased or absent for a considerable 23:24.250 --> 23:25.850 period of time. 23:26.030 --> 23:28.740 There is facial dip legia open their 23:28.740 --> 23:29.480 club feet, 23:29.490 --> 23:31.220 there is a relax at your diaphragm. 23:31.350 --> 23:33.900 The diaphragm Recently we had a 23:33.900 --> 23:36.840 child who was operated 23:36.850 --> 23:39.210 for a right side 23:39.220 --> 23:41.410 diaphragmatic hernia. 23:41.420 --> 23:44.330 And as I saw the child about a few weeks later and I 23:44.330 --> 23:45.060 saw the mother, 23:45.070 --> 23:47.680 I found out that it was one of these early on. 23:47.720 --> 23:48.650 My attorney. 23:48.660 --> 23:51.630 Dystrophy is to develop the psycho 23:51.630 --> 23:53.570 motor development is definitely dilated, 23:53.570 --> 23:56.440 It's mental retardation and the speech is 23:56.440 --> 23:57.060 slurred, 23:58.140 --> 24:00.920 no signs of neo Tonia in 24:00.930 --> 24:01.760 early infancy. 24:01.770 --> 24:04.670 This appears only after several months or 24:04.670 --> 24:05.670 several years. 24:06.140 --> 24:07.880 And interestingly enough, 24:07.890 --> 24:10.720 the mother is always the affected 24:10.730 --> 24:11.170 person, 24:11.170 --> 24:13.960 the one who gave the mutant gene to the child. 24:14.640 --> 24:15.560 There are in England. 24:15.560 --> 24:18.130 About 100 cases have been reported 24:18.130 --> 24:18.600 recently, 24:18.600 --> 24:20.600 I think in the february issue of the archive, 24:20.600 --> 24:23.440 diseases of childhood and all had an 24:23.440 --> 24:24.450 effective matter. 24:24.840 --> 24:25.050 Now. 24:25.050 --> 24:27.870 These are three of the eight families we have presently 24:27.870 --> 24:30.570 understanding and see in all of them the 24:30.570 --> 24:32.870 mother was the affected party. 24:32.880 --> 24:33.760 The father, 24:33.770 --> 24:36.690 if the father is affected with my 24:36.690 --> 24:39.130 alternate dystrophy gives the gene to his 24:39.140 --> 24:39.980 offspring. 24:39.990 --> 24:42.520 The mutant gene that is the child will 24:42.520 --> 24:45.040 not have early onset. 24:45.050 --> 24:46.170 My alternatives surface. 24:46.740 --> 24:47.620 In other words, 24:47.630 --> 24:50.150 we have here a most interesting 24:50.150 --> 24:52.820 combination and we can summarize the problem. 24:52.820 --> 24:55.590 Like this early onset maya 24:55.590 --> 24:56.090 Tonia, 24:56.090 --> 24:58.430 a trophic occurs in Children 24:58.440 --> 25:01.290 who inherit the mutant gene 25:01.300 --> 25:02.230 from their mother. 25:03.140 --> 25:04.330 Early onset. 25:04.330 --> 25:07.230 My atomic dystrophy does not occur in 25:07.230 --> 25:09.770 Children who inherit a wild type 25:09.770 --> 25:10.240 gene, 25:10.250 --> 25:13.020 the normal gene from their mother and early my 25:13.020 --> 25:15.370 attorney dystrophy does not occur in Children 25:15.380 --> 25:18.340 who inherit either the 25:18.350 --> 25:21.230 newton or the wild type gene from 25:21.230 --> 25:21.860 their father. 25:22.240 --> 25:23.340 In other words, 25:23.340 --> 25:24.920 then there seems, 25:24.930 --> 25:27.730 does it seems that the maya 25:27.730 --> 25:29.860 tonic atrophy of the mother 25:29.870 --> 25:32.750 creates during gestation and 25:32.760 --> 25:33.850 environment, 25:34.440 --> 25:37.200 which in combination with the 25:37.210 --> 25:39.790 Maya tonic dystrophy gene of the fetus 25:39.800 --> 25:42.480 causes the manifestations of early 25:42.490 --> 25:45.290 onset maya tonic maya Tonia, 25:45.290 --> 25:47.160 a tropical diatonic dystrophy. 25:47.170 --> 25:48.200 In other words, 25:48.210 --> 25:50.420 we have here a peculiar 25:50.420 --> 25:53.270 combination of nature nurture, 25:53.340 --> 25:54.960 which is terribly interesting. 25:55.140 --> 25:58.050 We don't know what the environmental sectors 25:58.060 --> 25:58.440 are. 25:58.450 --> 26:01.170 There is still time for research to find this out. 26:02.640 --> 26:03.440 Okay, 26:03.640 --> 26:04.060 now, 26:04.060 --> 26:05.760 let's see where we are. 26:11.040 --> 26:11.450 Yeah. 26:12.540 --> 26:12.860 Yeah. 26:13.840 --> 26:16.770 Now this child here 26:17.640 --> 26:20.560 came At the age 26:20.560 --> 26:22.620 of five months with diarrhea to the hospital. 26:22.620 --> 26:24.730 The attending physician called me and said, 26:24.740 --> 26:27.700 I believe I have a child with watnick Hoffman's disease. 26:27.710 --> 26:29.210 Come and see the child. 26:29.220 --> 26:30.690 I looked at the child. 26:30.700 --> 26:33.580 It was obviously very high 26:33.580 --> 26:34.850 park tonic, 26:35.240 --> 26:38.200 but I wasn't sure about 26:38.200 --> 26:39.580 what Nick Hoffman's disease. 26:39.590 --> 26:42.300 Now I was lucky enough to meet the mother 26:42.310 --> 26:43.360 at the bedside. 26:43.370 --> 26:45.740 This is the mother and she has a 26:45.750 --> 26:47.990 typical picture of 26:48.000 --> 26:50.180 Shark Omari 2s or 26:50.180 --> 26:52.560 peroneal muscular atrophy. 26:53.640 --> 26:54.270 No, 26:54.840 --> 26:57.580 the point I want to make is 26:57.590 --> 27:00.360 while most of the textbooks 27:00.370 --> 27:03.340 say that Shark 27:03.340 --> 27:05.670 Omari II's begins in the 27:05.670 --> 27:08.380 second or 3rd decade. 27:08.390 --> 27:10.730 We have quite a number of 27:10.730 --> 27:12.870 Children where the 27:12.870 --> 27:15.700 disease manifests as 27:15.700 --> 27:18.410 floppy penis in infancy as in this child 27:18.410 --> 27:21.360 here we studied in the family and you see here the 27:21.360 --> 27:21.920 pedigree, 27:21.930 --> 27:24.700 all the black signs here 27:24.710 --> 27:27.690 are individuals affected with 27:27.700 --> 27:28.910 my autonomic dystrophy. 27:28.920 --> 27:31.400 Those who have a little cross here have been 27:31.410 --> 27:33.370 examined by me personally, 27:33.390 --> 27:34.720 these three Children. 27:34.730 --> 27:36.450 This is our program here. 27:36.460 --> 27:37.370 This is his mother. 27:37.380 --> 27:40.260 She has since then a second child who is also hypothalamic 27:40.430 --> 27:42.020 and who has also 27:42.160 --> 27:45.120 delayed a motor 27:45.120 --> 27:47.050 nerve conduction velocity. 27:47.630 --> 27:50.410 These three Children here I visited them 27:50.410 --> 27:52.290 one sunday in Illinois. 27:52.300 --> 27:54.550 They all okay and 27:54.940 --> 27:56.820 presented the 27:56.830 --> 27:59.710 manifestations of infantile 27:59.720 --> 28:02.350 sloppiness of floppy penis during infancy. 28:02.940 --> 28:04.370 Their motor nerve conduction. 28:04.380 --> 28:05.430 When I saw them, 28:05.430 --> 28:08.140 they showed the typical picture of Charcot Marie tooth. 28:08.150 --> 28:11.050 I sent them to fill the dutch 28:11.060 --> 28:14.020 in ST louis Missouri who was kind 28:14.020 --> 28:16.570 enough to study their motor nerve conduction 28:16.570 --> 28:19.250 velocity and the diagnosis charco 28:19.260 --> 28:21.770 morita's was confirmed 28:22.140 --> 28:22.860 death. 28:23.440 --> 28:26.230 Let's keep in mind if 28:26.230 --> 28:28.360 you have a floppy infant, 28:28.740 --> 28:31.410 it may pay to 28:31.420 --> 28:34.160 order a motor nerve conduction velocity. 28:34.170 --> 28:36.860 You may find a shark of molecules disease. 28:37.440 --> 28:38.780 And on the other hand, 28:38.790 --> 28:41.660 if you have a family with Charcot 28:41.660 --> 28:42.680 Marie tooth disease, 28:42.690 --> 28:45.110 watch out for 28:45.120 --> 28:47.050 uh, 28:47.060 --> 28:49.460 for uh floppy infants. 28:49.940 --> 28:52.290 This pedigree here shows you a 28:52.300 --> 28:53.790 typical auto, 28:53.790 --> 28:55.710 so normal dominant inheritance, 28:55.710 --> 28:58.360 which is typical for 28:58.740 --> 29:01.720 a Charcot Marie 29:01.720 --> 29:02.420 tooth disease. 29:02.430 --> 29:05.040 And this brings me to the second 29:05.040 --> 29:07.280 part of this um 29:07.290 --> 29:08.890 presentation, 29:08.900 --> 29:11.060 namely genetic counseling. 29:11.440 --> 29:14.110 I could speak hours and hours about genetic 29:14.110 --> 29:16.480 counseling in neuromuscular disease. 29:16.790 --> 29:18.980 I don't do that and I limit 29:18.980 --> 29:21.440 myself to present to 29:21.440 --> 29:24.270 you some new discoveries 29:25.040 --> 29:27.190 in the realm of the most 29:27.200 --> 29:30.000 frequent of all neuromuscular 29:30.000 --> 29:30.690 diseases, 29:30.700 --> 29:33.350 namely Duchenne muscular dystrophy. 29:34.240 --> 29:37.010 Duchenne muscular dystrophy in my muscle clinic, 29:37.020 --> 29:39.810 which really presents a cross section through the 29:39.810 --> 29:40.550 state of Iowa. 29:40.550 --> 29:43.020 And it's not a selected material 29:43.030 --> 29:45.840 accounts for 70 of 29:45.850 --> 29:48.720 all our uh 29:48.730 --> 29:50.560 neuromuscular cases. 29:51.640 --> 29:51.910 Now, 29:51.910 --> 29:53.910 let's look at this situation here. 29:53.920 --> 29:55.960 Here we have a 29:55.970 --> 29:57.960 pedigree of a 29:58.340 --> 29:59.820 family restitution, 29:59.820 --> 30:00.950 muscular dystrophy. 30:00.960 --> 30:03.280 All the males which are 30:03.290 --> 30:05.740 squares and which are in black 30:05.750 --> 30:08.620 are or have been affected. 30:08.630 --> 30:10.460 Restitution muscular dystrophy. 30:10.940 --> 30:13.840 The female circles with three dots 30:13.850 --> 30:16.550 are geologically speaking, 30:17.340 --> 30:18.660 two carriers. 30:19.040 --> 30:20.710 And that's why they have three dots. 30:21.740 --> 30:22.410 You see here, 30:22.410 --> 30:23.120 for instance, 30:23.130 --> 30:23.960 the mother, 30:23.970 --> 30:26.910 This mother here has a brother who has muscular 30:26.910 --> 30:28.370 dystrophy and has one son. 30:28.380 --> 30:30.830 She has seven Children, 30:30.840 --> 30:31.940 which of course is five. 30:31.950 --> 30:34.200 Too many in view of the 30:34.210 --> 30:36.320 overcrowding of spaceship earth. 30:36.330 --> 30:36.490 Now, 30:36.490 --> 30:39.120 that's beside the Honoraria might give this free of 30:39.120 --> 30:39.850 charge. 30:39.860 --> 30:40.750 This advice. 30:41.240 --> 30:44.130 Now he came this 30:44.640 --> 30:47.600 and she came to the Master Clinic with that 30:47.600 --> 30:50.530 child here and I examined the child and I had a young 30:50.530 --> 30:53.480 resident with me and after the mother have lest she 30:53.480 --> 30:53.860 said, 30:54.440 --> 30:54.760 well, 30:54.770 --> 30:57.050 isn't mrs d not pregnant? 30:57.540 --> 30:57.830 Well, 30:57.840 --> 30:59.310 I didn't look at her belly. 30:59.310 --> 31:00.390 I looked at the child. 31:00.400 --> 31:03.240 So I ran after her and I found her in the 31:03.240 --> 31:03.650 corridor. 31:03.660 --> 31:06.110 I said mrs D are you pregnant? 31:06.120 --> 31:06.710 She says, 31:06.710 --> 31:07.420 yes I am. 31:07.430 --> 31:09.320 And I don't want to now. 31:09.320 --> 31:12.160 What does it mean for this lady who 31:12.160 --> 31:13.810 is geologically speaking, 31:13.820 --> 31:16.780 a proven true carrier of tradition, 31:16.780 --> 31:17.160 magical. 31:17.160 --> 31:17.950 This refugee. 31:18.540 --> 31:19.560 It means 31:21.340 --> 31:22.790 if her offspring, 31:22.790 --> 31:25.260 if the fetus is a female has only 31:25.270 --> 31:27.850 has two x chromosomes, 31:29.240 --> 31:31.590 one of the excess may Carry the mutant gene, 31:31.600 --> 31:34.480 there's a chance of 5050 for that and 31:34.490 --> 31:37.060 this may be a carrier pregnancy could go on. 31:37.640 --> 31:38.850 If however, 31:38.850 --> 31:41.580 the fetus has Only one 31:41.590 --> 31:42.770 x chromosome, 31:43.820 --> 31:45.060 it's probably a male. 31:45.440 --> 31:48.400 Then There is a 5050 chance that 31:48.400 --> 31:50.860 he may have been inherited the 31:50.860 --> 31:53.190 mutant gene from his mother and May 31:53.190 --> 31:55.270 develop Duchenne muscular dystrophy. 31:55.840 --> 31:56.810 So what we did, 31:56.820 --> 31:59.700 we sent her immediately to our obstetrician who didn't 31:59.700 --> 32:00.660 understand thesis. 32:00.670 --> 32:03.640 It was it happened to be a sex 32:03.640 --> 32:06.630 chroma teen negative vetoes, 32:06.640 --> 32:09.260 which means he had a 5050 chance 32:09.270 --> 32:11.560 of having um of 32:11.570 --> 32:13.960 developing Duchenne muscular dystrophy. 32:14.240 --> 32:17.130 We had to communicate this to the mother and give 32:17.130 --> 32:19.800 her the chances of uh the 32:19.800 --> 32:20.440 decision, 32:20.450 --> 32:23.170 whether she wants to take the risk and carry 32:23.170 --> 32:26.070 on or she wants to have a termination 32:26.070 --> 32:26.880 of the pregnancy. 32:26.890 --> 32:28.970 You genetically speaking, 32:28.980 --> 32:31.690 you genetically speaking this, 32:31.700 --> 32:34.600 uh this uh would be a 32:34.610 --> 32:37.550 termination of pregnancy would 32:37.560 --> 32:38.500 be justified. 32:38.510 --> 32:39.570 However, 32:39.580 --> 32:42.050 we never do this without. 32:42.440 --> 32:43.190 I mean, 32:43.200 --> 32:45.550 the decision is the parents, 32:45.560 --> 32:48.450 we can only give them the facts 32:48.460 --> 32:49.140 empty. 32:49.150 --> 32:51.820 Have to take the decision what they want to 32:51.820 --> 32:53.850 do by no means. 32:53.860 --> 32:56.810 Is it allowed to create a religious conflict for 32:56.810 --> 32:57.170 them? 33:00.340 --> 33:00.760 Now, 33:00.770 --> 33:03.740 let's just quickly look at this schematic 33:03.740 --> 33:04.660 drawing. 33:05.940 --> 33:08.920 Duchenne muscular dystrophy can be inherited 33:08.930 --> 33:10.370 through generations. 33:10.940 --> 33:13.630 And you see here the grandmother is a carrier, 33:13.730 --> 33:16.560 the mother is a carrier and the child has 33:16.570 --> 33:17.120 ambition, 33:17.120 --> 33:18.050 muscular dystrophy. 33:18.740 --> 33:19.300 It can, 33:19.300 --> 33:19.770 however, 33:19.770 --> 33:22.410 be that a point mutation took 33:22.410 --> 33:24.460 place when the mother was created 33:25.040 --> 33:27.260 and she would then be a carrier. 33:27.270 --> 33:29.700 Or it can be that the 33:29.710 --> 33:32.390 point mutation took place when the 33:32.400 --> 33:35.170 when the little boy was created. 33:35.840 --> 33:38.500 In about 2/3 of the cases of 33:38.510 --> 33:39.840 Duchenne Muscular dystrophy. 33:39.850 --> 33:42.560 This is the mechanism it is inherited in 33:42.560 --> 33:43.590 about 1/3. 33:43.600 --> 33:46.150 It is either a mutation in the mother or a 33:46.150 --> 33:47.450 mutation in the child. 33:48.340 --> 33:48.850 No, 33:49.740 --> 33:52.560 how can we this 33:52.560 --> 33:55.460 side whether a moderate carrier? 33:55.460 --> 33:56.770 See this model here. 33:57.240 --> 33:59.570 She may have A child with multiple dystrophy, 33:59.570 --> 34:00.490 his appointment Asian, 34:00.490 --> 34:03.250 but she can have other Children who will be perfectly normal. 34:03.260 --> 34:05.990 This model here has a chance for 34:06.000 --> 34:08.990 every male of spring of 5050 of 34:08.990 --> 34:10.480 having another affected boy. 34:10.490 --> 34:12.360 And the same is true for this mother here. 34:13.040 --> 34:13.420 Well, 34:14.340 --> 34:17.010 how can we decide 34:17.020 --> 34:19.870 whether a mother is a carrier or 34:19.870 --> 34:20.250 not. 34:21.040 --> 34:21.460 Now. 34:21.470 --> 34:24.220 Several various tests have 34:24.230 --> 34:26.260 been given To 34:26.270 --> 34:29.180 determine the carrier stage of the 34:29.180 --> 34:29.560 mother. 34:29.840 --> 34:31.260 I mentioned only two. 34:31.840 --> 34:34.550 Only two are really of practical importance 34:34.710 --> 34:37.600 namely Sarah correction, 34:38.070 --> 34:41.050 creatine for smokiness determination 34:41.050 --> 34:41.660 in the modern. 34:42.340 --> 34:45.260 The ask for three 34:46.250 --> 34:48.520 Samples on three different days. 34:48.940 --> 34:50.560 If the mean of trees, 34:50.570 --> 34:53.380 these three samples is above normal. 34:53.380 --> 34:54.770 In one of these ladies, 34:54.780 --> 34:57.480 we would consider her as a 34:57.490 --> 34:59.920 carrier of the muscular 34:59.930 --> 35:00.930 dystrophy gee. 35:00.960 --> 35:03.880 Of course we have to be sure that we 35:03.880 --> 35:06.750 do not overlook unspecific 35:06.760 --> 35:09.340 elevations of the CPK for instance, 35:09.340 --> 35:10.560 cardiomyopathy, 35:10.940 --> 35:12.210 Thyroid disorder, 35:12.600 --> 35:14.090 excessive exercise. 35:14.100 --> 35:17.010 If this mother runs 10 miles and she's 35:17.010 --> 35:18.000 not used to it, 35:18.940 --> 35:21.790 Then her CPK will be elevated for a 35:21.790 --> 35:22.440 few days. 35:22.510 --> 35:25.450 If she then runs everyday 10 miles and after 35:25.450 --> 35:28.360 six weeks she has achieved the respective training. 35:28.740 --> 35:31.560 Her CPK would no longer be elevated. 35:32.440 --> 35:33.360 We have also, 35:33.360 --> 35:36.300 if the CPK is elevated to think of families 35:36.300 --> 35:39.130 with malignant hypothermia as it was mentioned this 35:39.130 --> 35:41.200 morning or of muscular traumatised. 35:41.200 --> 35:41.320 Um, 35:41.320 --> 35:41.860 the other day, 35:41.860 --> 35:43.870 I had a lady who had a high 35:43.870 --> 35:45.000 CPK, 35:45.010 --> 35:47.970 I was worried about it and it came out that she had 35:47.970 --> 35:50.040 a big hematoma on her leg. 35:50.140 --> 35:52.860 She has fallen from her bicycle and at that time a duma 35:52.940 --> 35:55.790 which was responsible for her 35:55.800 --> 35:56.960 high CPK. 35:58.240 --> 35:58.750 No, 35:59.440 --> 36:00.550 in other words, 36:01.130 --> 36:03.870 if the sea became 36:04.010 --> 36:06.590 of such a mother or for that reason, 36:07.030 --> 36:07.470 um, 36:07.480 --> 36:10.210 of the sister of 36:10.220 --> 36:11.580 a dystrophy, 36:11.590 --> 36:14.080 Duchenne dystrophy patient is 36:14.090 --> 36:14.820 elevated. 36:14.830 --> 36:17.450 We are sure it is a carrier. 36:17.460 --> 36:18.950 However, 36:18.960 --> 36:21.800 only 60 36:21.810 --> 36:24.680 of the truth of the geologically proven 36:24.680 --> 36:27.230 carriers Have an elevated CPK 36:27.240 --> 36:29.400 means CPK three determination. 36:29.410 --> 36:31.160 40 percent have not. 36:31.630 --> 36:32.940 That means therefore, 36:32.950 --> 36:33.630 if we have, 36:33.630 --> 36:34.410 for instance, 36:34.550 --> 36:37.080 a sister of this little 36:37.080 --> 36:37.660 boy, 36:38.430 --> 36:38.960 uh, 36:39.630 --> 36:42.500 He she would have a 5050 36:42.500 --> 36:45.200 chance of inheriting mutant gene from the 36:45.200 --> 36:45.760 mother. 36:45.770 --> 36:47.780 That would mean um, 36:47.790 --> 36:49.270 50 Of, 36:49.280 --> 36:51.850 of 40 of the 40 where the 36:51.850 --> 36:53.050 CPK may be normal. 36:53.050 --> 36:54.380 In spite of carrier stage, 36:54.390 --> 36:56.950 she Would still have a 20 36:56.960 --> 36:59.950 percent chance of being a carrier 36:59.960 --> 37:01.050 of the mutant gene. 37:01.530 --> 37:02.060 Of course, 37:02.060 --> 37:05.000 that is the most unsatisfactory 37:05.010 --> 37:06.750 state of affair. 37:08.130 --> 37:10.740 For that reason we have in 37:10.750 --> 37:13.240 our laboratory developed an other 37:13.240 --> 37:13.880 test. 37:15.130 --> 37:17.900 It consists in the study 37:17.920 --> 37:19.740 of in vitro 37:19.750 --> 37:20.990 ribosomes, 37:20.990 --> 37:23.850 all protein synthesis of a muscle 37:23.860 --> 37:24.550 explained. 37:26.430 --> 37:27.290 In other words, 37:27.830 --> 37:30.670 if a doctor of a proven carrier, 37:30.670 --> 37:31.380 for instance, 37:31.390 --> 37:34.350 has a three normalcy 37:34.350 --> 37:35.000 pks, 37:36.830 --> 37:39.420 She still has a 20 risk of being a carrier. 37:39.630 --> 37:42.550 We would take a muscle biopsy of her. 37:42.930 --> 37:45.920 Would isolate from this muscle 37:45.920 --> 37:48.500 biopsy immediately after cooling it 37:48.510 --> 37:51.260 down to freezing point 37:51.270 --> 37:53.000 would immediately 37:53.010 --> 37:55.950 isolate the the 37:55.960 --> 37:58.550 ribosomes into various 37:58.550 --> 38:00.930 fractions the monem eric the police sonic, 38:00.930 --> 38:01.740 the heavy police, 38:01.750 --> 38:03.540 uh police rooms. 38:03.720 --> 38:06.290 And then by adding 38:06.360 --> 38:08.570 attacked amino acids, 38:08.570 --> 38:10.930 would study the ribosomes all 38:10.930 --> 38:12.260 protein sentences. 38:12.260 --> 38:13.040 In vitro, 38:13.820 --> 38:16.510 This test has proven to be 38:16.520 --> 38:18.550 98 percent reliable. 38:18.550 --> 38:21.350 We have so far checked about over 38:21.350 --> 38:23.880 100 to Geologically proven 38:23.880 --> 38:26.680 carriers and in 98 of 38:26.690 --> 38:28.580 them was the test. 38:28.590 --> 38:30.540 Reliably elevated. 38:30.550 --> 38:33.310 So we consider this as reliable 38:33.310 --> 38:36.070 enough to modify our genetic 38:36.080 --> 38:37.620 counseling accordingly. 38:38.220 --> 38:40.080 Now transfer technical purposes. 38:40.090 --> 38:42.060 Many of the M. 38:42.060 --> 38:42.420 D. 38:42.420 --> 38:42.830 A. 38:42.840 --> 38:45.480 Muscular dystrophy association of America chapters. 38:45.490 --> 38:47.160 Pay the trip. 38:47.170 --> 38:48.720 Empty expenses of the test, 38:48.720 --> 38:51.720 the test as we do it presently And we are trying to 38:51.720 --> 38:53.840 simplify $250. 38:54.620 --> 38:57.560 We like to have the lady to come 38:57.570 --> 39:00.380 up to do the biopsy in in our 39:00.380 --> 39:00.910 hospital. 39:00.920 --> 39:01.630 However, 39:01.630 --> 39:03.800 if this should not be feasible, 39:03.810 --> 39:06.550 if we could not ship the lady the lady to 39:06.550 --> 39:07.050 us, 39:07.060 --> 39:09.900 then you can ask for 39:09.910 --> 39:12.530 a container from us for like 39:12.620 --> 39:13.930 liquid nitrogen. 39:13.930 --> 39:16.700 We would send you such a container and you would 39:16.710 --> 39:19.240 meal the sample to us with 39:19.250 --> 39:21.820 special freed by 39:21.820 --> 39:22.940 notifying us. 39:22.950 --> 39:25.620 However we prefer it the 39:25.630 --> 39:26.450 first day. 39:28.620 --> 39:31.200 So in 39:31.200 --> 39:34.140 quintessence and if the rivals Roma protein synthesis 39:34.140 --> 39:34.900 is normal, 39:34.910 --> 39:37.700 we assume that this is not a carrier and we 39:37.710 --> 39:39.010 advise her accordingly. 39:39.020 --> 39:41.700 If the rivals Roma protein sentences in vitro is 39:41.700 --> 39:42.200 abnormal, 39:42.210 --> 39:43.230 she is a career. 39:43.820 --> 39:46.730 We are prone sooner or 39:46.730 --> 39:49.610 later to make an error on the basis of 39:49.620 --> 39:50.700 the lion principle. 39:50.710 --> 39:53.260 But I believe in this particular 39:53.270 --> 39:54.190 situation. 39:54.200 --> 39:56.700 The exception due to the lion 39:56.700 --> 39:58.660 principles would be 39:58.670 --> 40:00.440 exceedingly rare. 40:01.010 --> 40:03.830 Now what are we doing if a 40:03.830 --> 40:05.160 mother is a carrier? 40:06.910 --> 40:09.650 What are the possibilities for her 40:09.660 --> 40:11.940 with respect to her reproductive activity? 40:12.310 --> 40:15.290 One she could have a cuba ligation 40:15.290 --> 40:16.430 and adopt Children. 40:16.910 --> 40:18.240 That would be one solution. 40:19.510 --> 40:22.160 The second solution is that she takes the chance. 40:22.810 --> 40:24.940 That is the least good solution. 40:25.510 --> 40:28.510 And the third solution would be if there are 40:28.510 --> 40:31.440 no religious or ethical arguments 40:31.450 --> 40:33.830 against the possible termination of 40:33.830 --> 40:34.560 pregnancy. 40:34.570 --> 40:36.890 Prenatal sex determination by 40:36.900 --> 40:39.090 Amniocentesis is done during the 40:39.090 --> 40:41.530 14th to 16 weeks of 40:41.530 --> 40:44.230 pregnancy would be indicated. 40:46.610 --> 40:47.240 No. 40:48.310 --> 40:49.880 You may ask the question. 40:49.890 --> 40:52.550 Well now you have to still 40:52.560 --> 40:53.610 if It is a boy, 40:53.610 --> 40:56.510 if the sex determination reveals that it's a 40:56.510 --> 40:56.800 boy, 40:56.800 --> 40:59.750 there's still a 50 chance that the boy could 40:59.760 --> 41:00.330 be normal. 41:00.810 --> 41:01.230 Two. 41:02.710 --> 41:03.060 Well, 41:03.070 --> 41:04.260 next question then, 41:04.270 --> 41:06.130 are we able to 41:07.910 --> 41:10.670 to see whether the boy is affected or 41:10.670 --> 41:11.170 not? 41:11.810 --> 41:12.940 Whether he has, 41:13.170 --> 41:15.320 he will develop muscat disproportionate. 41:16.090 --> 41:17.500 The answer is no. 41:17.510 --> 41:18.140 Not yet. 41:18.510 --> 41:20.160 We are doing studies, 41:20.160 --> 41:22.160 we are trying to determine 41:22.170 --> 41:25.000 the number one the difficult 41:25.010 --> 41:27.990 culture the fetal cells in the amniotic fluid 41:27.990 --> 41:30.920 and see whether we can get any rivals Roma protein. 41:30.930 --> 41:33.400 This is sentences out of that that's still in the 41:33.400 --> 41:34.640 experimental stage. 41:35.210 --> 41:36.020 Likewise, 41:36.020 --> 41:37.900 in the experimental stage is G. 41:37.900 --> 41:38.160 P. 41:38.160 --> 41:38.830 K. 41:38.840 --> 41:41.140 Determination in the fetal blood. 41:42.210 --> 41:45.190 But here I have to say there is probably 41:45.200 --> 41:46.410 something in it. 41:46.410 --> 41:47.700 I don't know how much. 41:47.740 --> 41:50.110 But let me tell you that we have 41:50.110 --> 41:52.730 developed with Anthony in Chicago, 41:52.740 --> 41:55.570 a method where we can determine 41:55.580 --> 41:58.350 CPK in one drop of 41:58.360 --> 41:59.120 dried blood. 41:59.130 --> 42:02.080 So we could puncture the and get a drop 42:02.080 --> 42:05.000 of the fetal that and could see whether cPK is 42:05.000 --> 42:05.470 elevated. 42:05.480 --> 42:08.080 That is still under just the beginning 42:08.090 --> 42:09.310 to study. 42:09.600 --> 42:12.020 But that's another thing 42:12.400 --> 42:14.750 with this so called test. 42:14.760 --> 42:16.650 And let me tell you first test, 42:16.650 --> 42:17.110 we do. 42:17.600 --> 42:20.250 The test is the so called firefly 42:20.250 --> 42:20.670 test. 42:20.680 --> 42:20.920 Now, 42:20.930 --> 42:23.430 every student biochemistry knows the 42:23.430 --> 42:24.750 firefly test. 42:24.820 --> 42:27.570 I mean he does that what Anthony in 42:27.570 --> 42:28.700 Chicago has done. 42:28.710 --> 42:31.430 He has modified a test 42:31.900 --> 42:34.170 that he can do it in a drop of dried blood. 42:34.180 --> 42:35.300 Now what is the test? 42:35.570 --> 42:37.820 You know that CPK 42:38.300 --> 42:39.710 activates a. 42:39.710 --> 42:39.930 D. 42:39.930 --> 42:40.250 P. 42:40.250 --> 42:41.630 To 80 P. 42:41.640 --> 42:44.090 And 80 P activates the 42:44.090 --> 42:46.280 luciferase luciferians system, 42:46.280 --> 42:49.170 which is An extract from the tail of the 42:49.170 --> 42:52.150 firefly and gives a 42:52.150 --> 42:53.060 light reaction. 42:53.070 --> 42:55.650 Now the more CPK, 42:55.660 --> 42:57.190 the more 80p, 42:57.200 --> 42:58.610 the more 80 p. 42:58.620 --> 42:59.570 The more light. 42:59.580 --> 43:02.290 And we can measure by a simple light 43:02.300 --> 43:02.940 measurement. 43:02.950 --> 43:05.560 That is the semi quantitative method. 43:05.570 --> 43:08.330 We can express the light 43:08.330 --> 43:10.610 reaction in times normal. 43:11.200 --> 43:13.430 And it has shown that this test, 43:13.430 --> 43:16.100 which can be done in one drop of 43:16.110 --> 43:16.880 dried blood, 43:16.990 --> 43:18.160 not out of left, 43:18.170 --> 43:20.850 not out of left in one drop of my blood. 43:20.860 --> 43:22.970 And it has shown a pretty nice 43:22.970 --> 43:25.500 correlation between our routine C. 43:25.500 --> 43:25.690 P. 43:25.690 --> 43:26.060 K. 43:26.200 --> 43:26.600 C, 43:26.600 --> 43:29.600 for instance is our routine CPK is between 10,000 43:29.600 --> 43:30.880 and 12,000. 43:30.890 --> 43:33.710 The firefly test is 9200 times 43:33.710 --> 43:34.290 normal. 43:34.300 --> 43:37.220 If it is 3900 the 43:37.220 --> 43:39.970 firefly is 40 if it is within 43:39.970 --> 43:40.850 normal limits, 1216 00:43:40.860 --> aN:aN:000NaN 43:40.860 --> 43:44.810 25-120 43:44.810 --> 43:45.350 535, 43:45.360 --> 43:48.150 it is 1-2 times normal in 43:48.150 --> 43:48.950 the firefly. 43:48.960 --> 43:51.620 So that is really pretty good correlation. 43:53.400 --> 43:55.370 The question therefore 43:55.380 --> 43:58.310 arises whether or not 43:58.320 --> 44:01.250 we should use this test as a 44:01.250 --> 44:03.810 screening method for newborns. 44:04.990 --> 44:07.990 Then before we 44:07.990 --> 44:09.360 can do that, 44:09.370 --> 44:12.040 we have to answer 44:12.200 --> 44:14.880 the criteria for screening. 44:14.890 --> 44:15.720 They are 44:17.890 --> 44:19.050 screening is allowed. 44:19.050 --> 44:19.450 Then, 44:19.570 --> 44:20.110 eh, 44:20.590 --> 44:23.380 if the incidents of Duchenne muscular dystrophy is high 44:23.380 --> 44:25.920 enough to justify the test two, 44:26.290 --> 44:29.040 a CPK elevated already in the 44:29.040 --> 44:32.020 newborn who later on will develop Duchenne 44:32.020 --> 44:32.920 muscular dystrophy. 44:33.490 --> 44:35.630 You tend to answer the question, 44:35.640 --> 44:37.180 are there false negatives? 44:37.190 --> 44:38.920 Are their false positives? 44:39.390 --> 44:42.180 Is screening justified for Duchenne 44:42.180 --> 44:43.200 muscular dystrophy, 44:43.200 --> 44:46.120 thinks there is no cure for it 44:46.130 --> 44:47.250 available at the president. 44:47.250 --> 44:49.620 There's a treatment but no cure and 44:49.630 --> 44:50.790 finally, 44:50.800 --> 44:53.650 they can out just very recently. 44:53.660 --> 44:56.630 An important for our screening is 44:56.630 --> 44:59.580 that resources for follow up counselling are 44:59.590 --> 45:00.210 available. 45:00.790 --> 45:03.130 Let me quickly answer these 45:03.130 --> 45:03.870 questions. 45:03.880 --> 45:04.750 Number one, 45:04.750 --> 45:05.460 the incidents. 45:05.470 --> 45:06.110 Yes. 45:06.120 --> 45:07.040 The answer is yes. 45:07.370 --> 45:08.890 The incidence is between 45:08.890 --> 45:11.290 one and 1201 and 45:11.290 --> 45:14.110 3008 100 Life Born Boys. 45:14.120 --> 45:16.900 So that is much more frequent than piquet you for 45:16.900 --> 45:17.220 instance, 45:17.220 --> 45:20.000 for which we have testing by God, 45:20.000 --> 45:22.940 it's almost compulsory in almost every state of the 45:22.950 --> 45:23.310 union. 45:24.790 --> 45:27.520 Question two is the 45:27.520 --> 45:30.310 CPK already elevated in 45:30.310 --> 45:33.140 newborns who later on developed DND. 45:33.150 --> 45:35.290 The question is yes, 45:35.300 --> 45:36.080 most, 45:36.090 --> 45:37.310 probably yes, 45:38.990 --> 45:41.870 at least in all cases where in very early 45:41.870 --> 45:44.400 pre clinical stages CPK was tested, 45:44.410 --> 45:47.160 it was sky high Beckman tested vista 45:47.160 --> 45:49.970 firefly with our modified firefly tests, 45:49.980 --> 45:52.810 16,000 Newborn boys and found 45:52.810 --> 45:55.730 five times elevated CPK in 45:55.740 --> 45:56.120 each. 45:56.130 --> 45:58.610 He could find a 45:59.090 --> 46:00.910 um elevated CPK. 46:00.920 --> 46:03.330 We have recently this lady 46:03.330 --> 46:04.010 here, 46:04.020 --> 46:06.890 a 19 years old girl of whom I know Since 46:06.890 --> 46:09.630 10 years that she is a carrier but because she has 46:09.640 --> 46:12.560 elevated CPK she has an uncle and she has 46:12.560 --> 46:15.500 a brother who has Duchenne muscular dystrophy. 46:16.180 --> 46:16.990 Now the mother, 46:17.380 --> 46:19.670 this mother came with her son for examine, 46:19.670 --> 46:22.460 told me you know what And 46:22.470 --> 46:25.000 Eloise is just up in the delivery room delivering 46:25.680 --> 46:26.120 gee. 46:26.120 --> 46:28.710 I said that's horrible and I run up 46:29.180 --> 46:31.600 and lo and behold a little boy body. 46:32.580 --> 46:35.160 We did the CPK in this child. 46:35.170 --> 46:37.920 The firefly test was 105 times 46:37.920 --> 46:40.900 normal with it on the third day of life. 46:40.910 --> 46:43.630 A muscle biopsy and you see there is already a 46:43.640 --> 46:46.550 typical evidence of muscular dystrophy with 46:46.550 --> 46:47.930 varying fibers. 46:47.930 --> 46:50.840 Has looked at this huge fibers is rounding of 46:50.850 --> 46:51.460 the fibers, 46:51.470 --> 46:54.470 increased connective tissue in between 46:54.470 --> 46:57.110 the fibers and some fibers should already the 46:57.110 --> 46:59.090 generation also regeneration muslim, 46:59.280 --> 47:02.200 so and the CPK 47:02.210 --> 47:03.520 was very high, 47:03.530 --> 47:05.090 very highly elevated. 47:06.080 --> 47:06.590 No. 47:07.680 --> 47:08.700 Next questions. 47:08.710 --> 47:10.610 Are their false negatives. 47:10.620 --> 47:13.390 Are there Children who develop later on 47:13.400 --> 47:16.360 Duchenne muscular dystrophy and have a 47:16.360 --> 47:18.490 normal CPk at the part? 47:18.500 --> 47:20.100 We don't know yet. 47:20.680 --> 47:21.740 We believe. 47:21.750 --> 47:22.450 No, 47:22.460 --> 47:25.160 but we have to do the test for a number of years 47:25.160 --> 47:27.000 before we can answer this question. 47:27.780 --> 47:28.790 Next question. 47:28.800 --> 47:31.130 Are there false positives? 47:31.140 --> 47:32.020 Yes, 47:32.280 --> 47:33.990 there are false positive. 47:34.000 --> 47:36.850 Oh.5 of the three 47:36.850 --> 47:38.110 days old infant. 47:38.110 --> 47:39.070 And we have tested so far, 47:39.070 --> 47:41.680 about 3000 have slightly elevated 47:41.680 --> 47:42.410 CPK. 47:42.780 --> 47:43.590 However, 47:44.280 --> 47:44.960 Number one, 47:44.960 --> 47:47.430 the CPK was never As highly 47:47.430 --> 47:49.590 elevated that solution because this was 47:49.600 --> 47:52.410 3456 12 times higher than 47:52.410 --> 47:52.860 normal, 47:52.870 --> 47:55.760 but not 60 or 100 times higher. 47:55.770 --> 47:56.980 And secondly, 47:56.990 --> 47:57.710 if we, 47:57.720 --> 47:59.120 at the first or second, 47:59.130 --> 48:00.960 well baby checkup tested again, 48:00.960 --> 48:02.190 the CPK was normal. 48:02.770 --> 48:05.770 There may be false positives in Becker muscular 48:05.770 --> 48:08.340 dystrophy in benign congenital muscular 48:08.340 --> 48:08.980 dystrophy, 48:08.990 --> 48:10.810 in malignant hypothermia. 48:10.820 --> 48:11.140 This, 48:11.140 --> 48:12.230 we don't know yet. 48:12.240 --> 48:14.400 This has still to be studied. 48:16.570 --> 48:17.090 No, 48:17.870 --> 48:20.660 if the second CPK is still highly 48:20.670 --> 48:21.450 elevated, 48:21.460 --> 48:24.230 then there is definitely a 48:24.230 --> 48:26.980 possibility of uh 48:26.990 --> 48:28.900 of Duchenne muscular dystrophy. 48:28.910 --> 48:30.400 We would then do an E. 48:30.400 --> 48:30.570 M. 48:30.570 --> 48:31.090 G. 48:31.100 --> 48:31.880 If the E M. 48:31.880 --> 48:32.100 G. 48:32.100 --> 48:32.780 Is abnormal, 48:32.790 --> 48:34.750 this was done by Backman in his cases, 48:34.760 --> 48:37.650 then we would be pretty sure that this 48:37.650 --> 48:38.500 is addition. 48:38.670 --> 48:38.960 No, 48:38.960 --> 48:39.570 we wouldn't, 48:39.590 --> 48:41.760 it could be any other of the myopathy. 48:42.670 --> 48:44.370 And if the, 48:44.380 --> 48:46.250 if the CPK, 48:46.260 --> 48:48.200 if the MG would be normal, 48:48.210 --> 48:50.820 we would then advise a 48:50.820 --> 48:51.740 muscle biopsy. 48:51.750 --> 48:54.740 So if the second CPK dump Done 48:54.820 --> 48:57.240 at about six or 12 48:57.250 --> 49:00.030 weeks after birth is 49:00.030 --> 49:01.140 still elevated. 49:01.150 --> 49:03.480 there is a strong suggestion, 49:03.490 --> 49:05.900 so not 100% proving that it could be 49:05.910 --> 49:07.590 dishing muscular dystrophy. 49:09.770 --> 49:10.290 No, 49:10.970 --> 49:11.830 the question, 49:12.230 --> 49:15.110 the fact that there is no curative 49:15.120 --> 49:17.900 treatment for Duchenne muscular dystrophy. 49:18.370 --> 49:20.700 Does this justify 49:20.700 --> 49:22.930 screening To answer these 49:22.930 --> 49:23.750 questions? 49:23.760 --> 49:26.410 We sent questionnaires to 49:26.420 --> 49:28.940 medical personnel in the hospital and two 49:28.940 --> 49:31.140 parents of muscular dystrophy Children. 49:31.190 --> 49:33.780 We asked him if we could 49:33.790 --> 49:36.650 tell you at the time of birth or 49:36.650 --> 49:39.200 soon thereafter that your son will 49:39.200 --> 49:39.690 develop. 49:39.690 --> 49:40.890 Duchenne muscular dystrophy. 49:41.070 --> 49:43.830 Would you like to know it Of 49:43.840 --> 49:45.380 our over 1000 49:46.270 --> 49:48.940 questionnaires went to medical personnel in our 49:48.940 --> 49:49.530 hospital, 49:49.540 --> 49:52.200 90 said Yes 10 said 49:52.210 --> 49:52.590 no. 49:53.170 --> 49:55.990 We ask 41 parents with 49:56.000 --> 49:57.740 one decision muscular dystrophy, 49:57.750 --> 50:00.480 70 percent said yes and of 50:00.480 --> 50:03.470 15 parents would have more than one 50:03.480 --> 50:06.220 Destroy official decision muscular dystrophy 50:06.220 --> 50:08.280 child 80 said yes. 50:08.760 --> 50:10.770 So I think that's pretty good 50:12.660 --> 50:15.540 a suggestion that 50:15.550 --> 50:17.390 the test would be just 50:18.860 --> 50:19.880 now then we ask, 50:19.890 --> 50:22.460 well why did you say yes And these were the 50:22.460 --> 50:23.180 answers. 50:23.660 --> 50:25.980 We would have guided our son's 50:25.990 --> 50:28.790 interest in direction other than 50:28.790 --> 50:30.510 sports and physical activities. 50:30.520 --> 50:33.270 If we would have known advert that he will develop 50:33.280 --> 50:34.190 logical dystrophy, 50:34.760 --> 50:37.020 we would have selected another house, 50:37.040 --> 50:38.930 one story with rams, 50:38.930 --> 50:41.380 no steps with wider doors with better 50:41.380 --> 50:43.340 bathroom to circulate etcetera. 50:43.340 --> 50:44.270 With the future. 50:44.960 --> 50:47.550 We would have moved to a place with better 50:47.550 --> 50:50.270 educational facilities for handicapped Children 50:50.650 --> 50:52.690 than in the town where we are now. 50:53.260 --> 50:54.860 And very important, 50:54.870 --> 50:57.580 we would not have disciplined the 50:57.580 --> 50:59.840 child for frequent falling 50:59.850 --> 51:02.830 and stumbling as we did when he was 51:02.840 --> 51:04.180 23 years old child. 51:04.560 --> 51:07.220 So there you you send a 51:07.230 --> 51:09.470 guilt feeling of that particular 51:09.480 --> 51:10.320 parent. 51:10.330 --> 51:11.300 And finally, 51:11.310 --> 51:13.880 we could have prevented the birth of our other 51:13.890 --> 51:15.270 effective sons. 51:15.280 --> 51:16.680 And that is probably important. 51:16.690 --> 51:17.780 And here I would like to. 51:18.260 --> 51:21.030 We have in our muscle files presently 51:21.100 --> 51:23.870 170 cases of Duchenne 51:23.870 --> 51:26.660 muscular dystrophy in 144 sip 51:26.660 --> 51:27.100 ships, 51:27.110 --> 51:29.770 which means that 31 of them 51:29.890 --> 51:32.820 were born into families which had already 51:32.820 --> 51:33.250 a son. 51:33.250 --> 51:34.690 Restitution muscular dystrophy. 51:36.260 --> 51:39.240 They could have been 30 51:39.240 --> 51:39.770 17%%. 51:40.160 --> 51:42.490 They could have been prevented 51:42.960 --> 51:45.330 If we would have been able to make the 51:45.330 --> 51:48.230 diagnosis at birth and would have done 51:48.240 --> 51:51.210 perinatal testing for Duchenne muscular dystrophy by 51:51.210 --> 51:53.220 the firefly test carrier. 51:53.220 --> 51:54.320 Study in the matter, 51:54.330 --> 51:56.920 prenatal sex determination in subsequent 51:56.920 --> 51:59.710 pregnancy and termination of pregnancy if the 51:59.710 --> 52:01.560 foetus is sex comedy negative. 52:02.550 --> 52:03.060 No, 52:03.850 --> 52:06.590 if you Assume that in the United 52:06.590 --> 52:07.170 States, 52:07.180 --> 52:08.130 every year, 52:08.130 --> 52:10.870 there are about 400-600 boys 52:10.870 --> 52:12.330 born who have, 52:12.340 --> 52:13.990 who will develop vision, 52:13.990 --> 52:15.050 muscular dystrophy. 52:15.070 --> 52:16.510 And if you assume that 52:16.510 --> 52:19.170 17.7 have 52:19.170 --> 52:21.560 already an older brother institution must be so, 52:21.560 --> 52:23.610 which would therefore be preventable. 52:23.620 --> 52:25.430 If we diagnose the 1st 1, 52:25.600 --> 52:27.910 we could prevent 70 to 52:27.910 --> 52:30.360 150 cases of titian 52:30.360 --> 52:33.280 muscular dystrophy per year in the United 52:33.280 --> 52:33.720 States. 52:33.940 --> 52:36.810 That would by truly 52:36.820 --> 52:38.880 and indeed be a blessing. 52:39.850 --> 52:40.680 However, 52:41.450 --> 52:43.910 if we consider the cost of treatment, 52:43.920 --> 52:45.410 the prevention of 100 G. 52:45.410 --> 52:45.550 M. 52:45.550 --> 52:45.720 D. 52:45.720 --> 52:45.910 K. 52:45.910 --> 52:48.280 Possibly the tragedy for the family, 52:48.290 --> 52:51.160 it's screening would be certainly uh 52:51.170 --> 52:51.800 justified. 52:51.810 --> 52:53.060 However, 52:53.450 --> 52:56.350 there are people for whom the 52:56.360 --> 52:58.880 care of a severe Duchenne muscular 52:58.890 --> 53:01.760 dystrophy child means a fulfillment. 53:02.250 --> 53:04.990 Are we permitted to prevent them from 53:04.990 --> 53:06.270 such experience? 53:06.280 --> 53:08.490 How can we predict success points? 53:08.500 --> 53:09.700 Ladies and gentlemen, 53:09.710 --> 53:12.010 that is up to you to decide. 53:12.020 --> 53:13.560 Thank you very much?