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Spinal cord, peripheral nerves & myasthemia
199
Two Cases of Adrenoleukodystrophy Diagnosed by Increased Serum Hexacosanoic Acid
Hiroyuki Ida, MD, Toshikatu Eto, MD and Kihei Maekawa,MD Department of Pediatrics, The likei University School of Medicine, Tokyo Adrenoleukodystrophy (ALD) can be diagnosed by electron microscopic examination of skin, conjunctival or adrenal biopsies or increased hexacosanoic acid of cultured skin fibroblast. But, both methods are invasive and difficult. This report demonstrated that analysis of serum free fatty acids is useful for a diagnosis of ALD.
Methods and Materials Two patients were suspected as ALD by clinical symptoms and brain CT scan. Total lipids were extracted by C:M (2:1, v/v) from 2 ml serum. Free fatty acids were extracted by hexan from total lipids and analyzed by gas liquid chromatography equiped with 3% OV-l column. Results In two patients, hexacosanoic acid (C 26 : 0 ) content was increased ; C 26:0/C22:0 ratio in patients was about 7 times as high as in control. Discussion ALD is suspected by clinical features, brain CT scan and diagnosed by electron microscopic examination and free fatty acids analysis from cultured skin fibroblast. But, final diagnosis is difficult before death. We clearly demonstrated that the analysis of serum very long saturated fatty acids is useful for a diagnosis of ALD. Furthermore, serum free fatty acids analysis by gas liquid chromatography is simple and less time consuming. Key words: Adrenoleukodystrophy, gas liquid chromatography, serum very long saturated fatty acids.
200 Four Cases of Hereditary Motor and Sensory Neuropathy in Childhood-Light and Electron Microscopic Studies of Sural Nerve Biopsies
Yoko Sugie, MD, Michiko Hara, MD, Moriichi Sugama, MD, Shinobu Kosaka, MD, Tomio Shibuya, MD, Hideo Sugie, MD, Keiko Shishikura, MD, Makiko Ohsawa, MD, Haruko Suzuki, MD and Yukio Fukuyama,MD Department of Pediotrics, Tokyo Women's Medical Col/ege, Tokyo
Two cases (cases 1 and 2) of hereditary motor and sensory neuropathy (HMSN) type 1 and two cases (cases 3 and 4) of HMSN type 2 were described. All cases were male and aged from 3y5m to 11 y 11m with the onset in early childhood. Cases I and 2 were siblings whose father was also similarly affected, suggesting autosomal dominant inheritance. However case 2, the younger brother of case 1, was still in the subclinical state. Cases 3 and 4 were sporadic and not related to each other. Muscle weakness and wasting were noticed below the knee, especially in the peroneal muscle group, in cases 1, 3 and 4. Distal portions of upper extremities were also affected and sensory disturbance was noticed in case 4. Motor conduction velocities were considerably decreased in cases 1 and 2, mildly decreased in case 3, and normal in case 4. Sensory conduction velocities were mildly decreased in cases 1, 2 and 3, and normal in case 4 . Neurogenic potentials were detected in all cases with EMG. Pathological studies including light and electron microscopic observations, fiber testing and morphometry of sural nerve biopsy material from cases 1, 2 and 3 were performed. A remarkable decrease of myelinated fiber density with a unimodal type of histogram , segemental de/remyelination, and some fibers with active axonal degeneration were found in both cases 1 and 2. Case 3 showed mild irregularity of the myelin sheath as the main pathological change, and myelinated fiber diameter analysis revealed a unimodal pattern with loss of large myelinated fibers. Ouvrier et al (1981) reported 11 cases of HMSN with rapidly progressive clinical courses. Both pathologically and electrophysiologically, they were different from HMSN type 3. Axonal degeneration affecting both myelinated and unmyelinated fibers was the main change in their cases. From the clinical description, we could not distinguish HMSN type 2 from the severe form of HMSN reported by Ouvrier, especially in the early stage. Our case 4 might be consistent with Ouvrier's cases, although sural nerve biopsy material was not obtained in case 4 .
Key words: Hereditary neuropathy, sural nerve biopsy, demyelination, onion bulb.
246 Brain & Development, Vol 6, No 2, 1984
201
202
Three Cases of Hereditary Motor and Sensory Neuropathy in a Family (HMSN Type III)
A Case of Congenital Hypomyelination Polyneuropathy
Hideaki Kudo, MD, Masahiro Terada, MD , Tomoko Abe, MD, Haruko Naito, MD, Kenji Nihei, MD and !kuya Nonaka, MD Department of Neurology, National Children's Hospital, Tokyo (HK, MT, TA, HN, KN); National Center for Nervous, Mental and Muscualr Disorders, Kodaira, Tokyo (IN)
Seijiro Asoh, MD , Tamiko Takemura , MD, Kiy oharu Inoue, MD and Nobuko Misugi, MD Departments of Pediatrics (SA) and Pathology (TT), Japanese Red Cross Medical Center, Tokyo; Department of Neurology, University of Tokyo, Tokyo (KI) ; Department of Orthopedic Surgery, Kanagawa Children's Medical Center, Yokohama, Kanagawa (NM)
Hereditary motor and sensory neuropathy (HMSN) is a rare disorder, consisting of a heterogeneous etiology . We experienced three patients with HMSN in a family , whose clinical pictures resembled HMSN type III, and reported clinicopathological findings of these cases.
A 10-year-old girl with congenital hypomyelination polyneuropathy was presented. She was the first-born child of unrelated parents and there was no family history of neuromuscular disease. She was uneventfully born at about 41 weeks gestation with a birth weight of 3.3 kg . She had head control at 4 months of age and was able to sit without support at 7 months of age. Her motor development seemed to be normal around that time. Thereafter, motor development was gradually retarded. She could not stand with support until 16 months of age and could not walk holding onto furniture until 18 months of age. At the age of 2 years 11 months, she was admitted to another hospital for neurological examination, and a possible diagnosis of Dejerine-Sottas disease was made. She could walk with a short leg brace at 3Y2 years of age and could walk alone at age of 4% years. At the age of 10 years 5 months, she was admitted to our hospital for more complete examination. Her intelligence was normal. The cranial nerves appeared normal. She could walk alone, but showed a wide-based ataxic gait. There was mild muscle wasting and weakness in distal parts of extremities. Deep tendon reflexes were completely absent. Vibration and position senses were severely affected. Romberg's sign was positive. There was no peripheral nerve hypertrophy. Laboratory findings were normal as to routine blood and urine examination. The CSF contained 2 lymphocytes per cubic millimeter, 54 mgldl of glucose and 60 mgjdl of protein. Motor nerve conduction velocity of the ulnar nerve was 2.2 m/sec, and the velocity of the posterior tibial nerve was unmeasurable. Electron microscope findings of the sural nerve biopsy confirmed the virtual absence of myelin sheaths of myelinated fibers. In some places, there was a thin myelin sheath. The "onion-bulbs" consisted of multiple layered empty basement membranes. Axons appeared to be normal. Myelin ovoid and band of Biingner were not observed. In recent years there have been several reports of congenital neuropathies. Microscopic examination of the peripheral nerves showed the absence of myelin sheaths without myelin degeneration products, and the disease entity of congenital hypomyelination polyneuropathy has been proposed. Our case is histologically similar to the above cases, and is considered to be a type of congenital hypomyelination polyneuropathy.
Case Report The family history revealed strong consanguinity; the mothers of cases 1 and 2, and case 3 were sisters, whilst the fathers of cases 1 and 2 and case 3 were cousins. The parents of cases 1 and 2 were cousins and so were those of case 3. Case 1, a 3 years 7 months old female showed retarded motor development since infancy . She was admitted to our hospital because of unsteady gait and slow movement. Neurological examination revealed generalized hypotonia, areflexia and sensory disturbance of touch and vibration in distal extremities. MCV was not measurable in all the examined nerves. Case 2, a female of 1 year 6 months old, could stand and walk with support, but was unable to walk by herself. Her neurological findings, except the markedly delayed MCV (median nerve, 2.4 m/s; tibial nerve, 3.4 m/s), were almost the same as those of case 1. Case 3, a 7 y aers 8 months old male, whose motor development had also been retarded since infancy, could run but only slowly. He was the cousin of cases 1 and 2. His neurological findings' were the same as those of cases 1 and 2. In the cervical region, hypertrophic great auricular nerves' were clearly visible. CSF protein was elevated in all cases. Auditory evoked brain stem responses (BSR) showed a delay in the latency of every wave unvaryingly . Sural nerve biopsy specimens from cases 1 and 3 showed severe loss of the myelin sheath, whilst no onion bulb formation was observed. Electron microscopically, the double layered redundant basement membrane of Schwann cells was striking. Neither active degeneration of myelin, nor axonal degeneration was observed. Cluster formati on was hardly seen. Conclusion The reported cases were clinically compatible with classical HMSN type III (Dejerine-Sottas disease) . Pathological findings of sural nerves, however, lacked interstitial hypertrophy, whereas myelin loss was remarkable. The conclusion, whether these cases should be classified as HMSN III or another entity of neuropathy such as congenital hypomyelination neuropathy, must await further evidence. Key words: Hereditary motor and sensory neuropathy, Dejerin-Sottas disease, congenital hypo myelination neuropathy.
Key words: Congenital hypomyelination polyneuropathy, absence of myelin, ataxic gait, electron microscope.
Brain & Development, Vol 6, No 2,1984 24 7
203 Sensory and Motor Neuropathy in Childhood
Nobuko Misugi, MD, Hiroko Iwamoto, MD, Michiko Hayashi, MD and Shouta Miyake, MD Departments of Orthopedics (NM) and Neurology (HI, MH, SM), Kanagawa Children's Medical Center, Yokohama, Kanagawa Many reports of chronic sensory and motor neuropathy of the adult type have been published. But work on the childhood type has been very limited. This report concerns clinical, electrophysiological and pathological findings in 18 infantile and childhood cases of chronic sensory and motor neuropathy which was not associated with any metabolic or other neurologic disorders. Materials and Methods The patients consisted of 9 males and 9 females. Their ages at the first examination ranged from under 1 year to 12 years. The patients have been followed for I to 13 years. Examinations included periodical electrophysiological examinations, sensory nerve biopsies (6 cases), the material being studied by the teased fiber method and subjected to fiber density determination, and muscle biopsies (9 cases). Results The patients were divided into 3 groups according to the rate of motor nerve conduction velocity (MCV) of the median nerve. Namely, Group I (MCV under 10 m/sec) 6 cases, Group II (MCV over 10 m/sec to subnormal) 8 cases, and Group III (normal MCV) 4 cases. Each of these groups appears to have characteristic symptoms and nerve pathology, respectively. Group I showed hypomyelination of the sural nerve and marked elevation of protein in the CSF which was not found in Groups II and III. Group II showed a decreased number of myelinated fibers, especially of the fibers of large diameter. Group III showed a deficit of large myelinated fibers but the total number of myelinated fibers did not appear to decrease. Onion bulb formation, a sign of demyelination and remyelination, was found in all groups but was more frequent in Groups II and III. Axonal degeneration was not found at all except in one case of Group I. Conclusion Prognosis of Group I, which corresponds to the type III of hereditary motor and sensory neuropathy (HMSN) of Dyck or the Dejerine-Sottas type, is poor, because trunk muscles are involved at an early stage and scoliosis and respiratory distress may appear. In Group II which probably belongs to HMSN I or the Charcot-Marie-Tooth type, proximal muscle power is preserved for a long period and prognosis is relatively good. In Group III, which shows no delay of MCV, HMSN II, good prognosis is maintained by wearing of braces and ankle joint operation. Key words: Chronic sensory and motor neuropathy, nerve biopsy, nerve conduction velocity, prognosis.
248 Brain & Development, Vol 6, No 2, 1984
204 Congenital Myasthenia Associated with Skeletal Abnormalities and Cataract in Two Sisters
Jchiro Okabe, MD, Shigeichi Kobayashi, MD and Shigehiko Kamoshita, MD. Department of Pediatrics, Jichi Medical School, Kawachi, Tochigi
In about 1% of patients with myasthenia gravis, symptoms are present at birth or shortly thereafter. In 1949 Levin described a variety of myasthenia gravis which he called "congenital myasthenia." The common features of this entity seem to be (1) a lack of myasthenia in the mother, (2) occurrence of the disease in siblings, (3) presence of symptoms at birth or shortly thereafter, (4) confinement of symptoms mostly to the extraocular muscles, and (5) no or only slight progression of the disease. The purpose of this report is to describe two sisters with congenital myasthenia associated with skeletal abnormalities and cataract. Case Reports Case 1 is a 13-year-old girl, whose younger sister is similarly affected (Case 2). The parents are well, and not consanguineous. She had bilateral ptosis from birth. The parents consulted a pediatrician when she was 1 year and 8 months, and a diagnosis of myasthenia gravis was made with the Tensilon test. She was floppy, and started to walk at the age of 6 years. She showed chest deformity since birth, and scoliosis was noted at the age of 7 years. Case 2 is 7-year-old. She also had bilateral ptosis from birth, and had measles encephalitis at the age of 6 months. She was also floppy and started to walk at the age of 3 years and 6 months. Examination They showed bilateral ptosis, a high arched palate, chest deformity, and scoliosis. There was weakness of the proximal muscles. There was no clinical improvement of ptosis after Tensilon injection. But repetitive ulnar nerve stimulation at a rate of 5 per second showed progressive diminution of the amplitude. This effect was reversed by intravenous Tensilon. Anti-acetylcholine receptor antibodies were not detected in either case. Histological studies of biopsied muscle (Case I: Quadriceps femoris, Case 2: Biceps brachii) showed mild variation in fiber size with normal fiber type distribution. There was punctated cataract in both cases. The IQ was 91 in the older sister, and 45 in the younger one. This familial incidence suggests an autosomal recessive heredity. Key words: Congenital myasthenia, skeletal abnormalities, cataract.
Two Cases of Adrenoleukodystrophy Diagnosed by Increased Serum Hexacosanoic Acid
Hiroyuki Ida, MD, Toshikatu Eto, MD and Kihei Maekawa,MD Department of Pediatrics, The likei University School of Medicine, Tokyo Adrenoleukodystrophy (ALD) can be diagnosed by electron microscopic examination of skin, conjunctival or adrenal biopsies or increased hexacosanoic acid of cultured skin fibroblast. But, both methods are invasive and difficult. This report demonstrated that analysis of serum free fatty acids is useful for a diagnosis of ALD.
Methods and Materials Two patients were suspected as ALD by clinical symptoms and brain CT scan. Total lipids were extracted by C:M (2:1, v/v) from 2 ml serum. Free fatty acids were extracted by hexan from total lipids and analyzed by gas liquid chromatography equiped with 3% OV-l column. Results In two patients, hexacosanoic acid (C 26 : 0 ) content was increased ; C 26:0/C22:0 ratio in patients was about 7 times as high as in control. Discussion ALD is suspected by clinical features, brain CT scan and diagnosed by electron microscopic examination and free fatty acids analysis from cultured skin fibroblast. But, final diagnosis is difficult before death. We clearly demonstrated that the analysis of serum very long saturated fatty acids is useful for a diagnosis of ALD. Furthermore, serum free fatty acids analysis by gas liquid chromatography is simple and less time consuming. Key words: Adrenoleukodystrophy, gas liquid chromatography, serum very long saturated fatty acids.
200 Four Cases of Hereditary Motor and Sensory Neuropathy in Childhood-Light and Electron Microscopic Studies of Sural Nerve Biopsies
Yoko Sugie, MD, Michiko Hara, MD, Moriichi Sugama, MD, Shinobu Kosaka, MD, Tomio Shibuya, MD, Hideo Sugie, MD, Keiko Shishikura, MD, Makiko Ohsawa, MD, Haruko Suzuki, MD and Yukio Fukuyama,MD Department of Pediotrics, Tokyo Women's Medical Col/ege, Tokyo
Two cases (cases 1 and 2) of hereditary motor and sensory neuropathy (HMSN) type 1 and two cases (cases 3 and 4) of HMSN type 2 were described. All cases were male and aged from 3y5m to 11 y 11m with the onset in early childhood. Cases I and 2 were siblings whose father was also similarly affected, suggesting autosomal dominant inheritance. However case 2, the younger brother of case 1, was still in the subclinical state. Cases 3 and 4 were sporadic and not related to each other. Muscle weakness and wasting were noticed below the knee, especially in the peroneal muscle group, in cases 1, 3 and 4. Distal portions of upper extremities were also affected and sensory disturbance was noticed in case 4. Motor conduction velocities were considerably decreased in cases 1 and 2, mildly decreased in case 3, and normal in case 4. Sensory conduction velocities were mildly decreased in cases 1, 2 and 3, and normal in case 4 . Neurogenic potentials were detected in all cases with EMG. Pathological studies including light and electron microscopic observations, fiber testing and morphometry of sural nerve biopsy material from cases 1, 2 and 3 were performed. A remarkable decrease of myelinated fiber density with a unimodal type of histogram , segemental de/remyelination, and some fibers with active axonal degeneration were found in both cases 1 and 2. Case 3 showed mild irregularity of the myelin sheath as the main pathological change, and myelinated fiber diameter analysis revealed a unimodal pattern with loss of large myelinated fibers. Ouvrier et al (1981) reported 11 cases of HMSN with rapidly progressive clinical courses. Both pathologically and electrophysiologically, they were different from HMSN type 3. Axonal degeneration affecting both myelinated and unmyelinated fibers was the main change in their cases. From the clinical description, we could not distinguish HMSN type 2 from the severe form of HMSN reported by Ouvrier, especially in the early stage. Our case 4 might be consistent with Ouvrier's cases, although sural nerve biopsy material was not obtained in case 4 .
Key words: Hereditary neuropathy, sural nerve biopsy, demyelination, onion bulb.
246 Brain & Development, Vol 6, No 2, 1984
201
202
Three Cases of Hereditary Motor and Sensory Neuropathy in a Family (HMSN Type III)
A Case of Congenital Hypomyelination Polyneuropathy
Hideaki Kudo, MD, Masahiro Terada, MD , Tomoko Abe, MD, Haruko Naito, MD, Kenji Nihei, MD and !kuya Nonaka, MD Department of Neurology, National Children's Hospital, Tokyo (HK, MT, TA, HN, KN); National Center for Nervous, Mental and Muscualr Disorders, Kodaira, Tokyo (IN)
Seijiro Asoh, MD , Tamiko Takemura , MD, Kiy oharu Inoue, MD and Nobuko Misugi, MD Departments of Pediatrics (SA) and Pathology (TT), Japanese Red Cross Medical Center, Tokyo; Department of Neurology, University of Tokyo, Tokyo (KI) ; Department of Orthopedic Surgery, Kanagawa Children's Medical Center, Yokohama, Kanagawa (NM)
Hereditary motor and sensory neuropathy (HMSN) is a rare disorder, consisting of a heterogeneous etiology . We experienced three patients with HMSN in a family , whose clinical pictures resembled HMSN type III, and reported clinicopathological findings of these cases.
A 10-year-old girl with congenital hypomyelination polyneuropathy was presented. She was the first-born child of unrelated parents and there was no family history of neuromuscular disease. She was uneventfully born at about 41 weeks gestation with a birth weight of 3.3 kg . She had head control at 4 months of age and was able to sit without support at 7 months of age. Her motor development seemed to be normal around that time. Thereafter, motor development was gradually retarded. She could not stand with support until 16 months of age and could not walk holding onto furniture until 18 months of age. At the age of 2 years 11 months, she was admitted to another hospital for neurological examination, and a possible diagnosis of Dejerine-Sottas disease was made. She could walk with a short leg brace at 3Y2 years of age and could walk alone at age of 4% years. At the age of 10 years 5 months, she was admitted to our hospital for more complete examination. Her intelligence was normal. The cranial nerves appeared normal. She could walk alone, but showed a wide-based ataxic gait. There was mild muscle wasting and weakness in distal parts of extremities. Deep tendon reflexes were completely absent. Vibration and position senses were severely affected. Romberg's sign was positive. There was no peripheral nerve hypertrophy. Laboratory findings were normal as to routine blood and urine examination. The CSF contained 2 lymphocytes per cubic millimeter, 54 mgldl of glucose and 60 mgjdl of protein. Motor nerve conduction velocity of the ulnar nerve was 2.2 m/sec, and the velocity of the posterior tibial nerve was unmeasurable. Electron microscope findings of the sural nerve biopsy confirmed the virtual absence of myelin sheaths of myelinated fibers. In some places, there was a thin myelin sheath. The "onion-bulbs" consisted of multiple layered empty basement membranes. Axons appeared to be normal. Myelin ovoid and band of Biingner were not observed. In recent years there have been several reports of congenital neuropathies. Microscopic examination of the peripheral nerves showed the absence of myelin sheaths without myelin degeneration products, and the disease entity of congenital hypomyelination polyneuropathy has been proposed. Our case is histologically similar to the above cases, and is considered to be a type of congenital hypomyelination polyneuropathy.
Case Report The family history revealed strong consanguinity; the mothers of cases 1 and 2, and case 3 were sisters, whilst the fathers of cases 1 and 2 and case 3 were cousins. The parents of cases 1 and 2 were cousins and so were those of case 3. Case 1, a 3 years 7 months old female showed retarded motor development since infancy . She was admitted to our hospital because of unsteady gait and slow movement. Neurological examination revealed generalized hypotonia, areflexia and sensory disturbance of touch and vibration in distal extremities. MCV was not measurable in all the examined nerves. Case 2, a female of 1 year 6 months old, could stand and walk with support, but was unable to walk by herself. Her neurological findings, except the markedly delayed MCV (median nerve, 2.4 m/s; tibial nerve, 3.4 m/s), were almost the same as those of case 1. Case 3, a 7 y aers 8 months old male, whose motor development had also been retarded since infancy, could run but only slowly. He was the cousin of cases 1 and 2. His neurological findings' were the same as those of cases 1 and 2. In the cervical region, hypertrophic great auricular nerves' were clearly visible. CSF protein was elevated in all cases. Auditory evoked brain stem responses (BSR) showed a delay in the latency of every wave unvaryingly . Sural nerve biopsy specimens from cases 1 and 3 showed severe loss of the myelin sheath, whilst no onion bulb formation was observed. Electron microscopically, the double layered redundant basement membrane of Schwann cells was striking. Neither active degeneration of myelin, nor axonal degeneration was observed. Cluster formati on was hardly seen. Conclusion The reported cases were clinically compatible with classical HMSN type III (Dejerine-Sottas disease) . Pathological findings of sural nerves, however, lacked interstitial hypertrophy, whereas myelin loss was remarkable. The conclusion, whether these cases should be classified as HMSN III or another entity of neuropathy such as congenital hypomyelination neuropathy, must await further evidence. Key words: Hereditary motor and sensory neuropathy, Dejerin-Sottas disease, congenital hypo myelination neuropathy.
Key words: Congenital hypomyelination polyneuropathy, absence of myelin, ataxic gait, electron microscope.
Brain & Development, Vol 6, No 2,1984 24 7
203 Sensory and Motor Neuropathy in Childhood
Nobuko Misugi, MD, Hiroko Iwamoto, MD, Michiko Hayashi, MD and Shouta Miyake, MD Departments of Orthopedics (NM) and Neurology (HI, MH, SM), Kanagawa Children's Medical Center, Yokohama, Kanagawa Many reports of chronic sensory and motor neuropathy of the adult type have been published. But work on the childhood type has been very limited. This report concerns clinical, electrophysiological and pathological findings in 18 infantile and childhood cases of chronic sensory and motor neuropathy which was not associated with any metabolic or other neurologic disorders. Materials and Methods The patients consisted of 9 males and 9 females. Their ages at the first examination ranged from under 1 year to 12 years. The patients have been followed for I to 13 years. Examinations included periodical electrophysiological examinations, sensory nerve biopsies (6 cases), the material being studied by the teased fiber method and subjected to fiber density determination, and muscle biopsies (9 cases). Results The patients were divided into 3 groups according to the rate of motor nerve conduction velocity (MCV) of the median nerve. Namely, Group I (MCV under 10 m/sec) 6 cases, Group II (MCV over 10 m/sec to subnormal) 8 cases, and Group III (normal MCV) 4 cases. Each of these groups appears to have characteristic symptoms and nerve pathology, respectively. Group I showed hypomyelination of the sural nerve and marked elevation of protein in the CSF which was not found in Groups II and III. Group II showed a decreased number of myelinated fibers, especially of the fibers of large diameter. Group III showed a deficit of large myelinated fibers but the total number of myelinated fibers did not appear to decrease. Onion bulb formation, a sign of demyelination and remyelination, was found in all groups but was more frequent in Groups II and III. Axonal degeneration was not found at all except in one case of Group I. Conclusion Prognosis of Group I, which corresponds to the type III of hereditary motor and sensory neuropathy (HMSN) of Dyck or the Dejerine-Sottas type, is poor, because trunk muscles are involved at an early stage and scoliosis and respiratory distress may appear. In Group II which probably belongs to HMSN I or the Charcot-Marie-Tooth type, proximal muscle power is preserved for a long period and prognosis is relatively good. In Group III, which shows no delay of MCV, HMSN II, good prognosis is maintained by wearing of braces and ankle joint operation. Key words: Chronic sensory and motor neuropathy, nerve biopsy, nerve conduction velocity, prognosis.
248 Brain & Development, Vol 6, No 2, 1984
204 Congenital Myasthenia Associated with Skeletal Abnormalities and Cataract in Two Sisters
Jchiro Okabe, MD, Shigeichi Kobayashi, MD and Shigehiko Kamoshita, MD. Department of Pediatrics, Jichi Medical School, Kawachi, Tochigi
In about 1% of patients with myasthenia gravis, symptoms are present at birth or shortly thereafter. In 1949 Levin described a variety of myasthenia gravis which he called "congenital myasthenia." The common features of this entity seem to be (1) a lack of myasthenia in the mother, (2) occurrence of the disease in siblings, (3) presence of symptoms at birth or shortly thereafter, (4) confinement of symptoms mostly to the extraocular muscles, and (5) no or only slight progression of the disease. The purpose of this report is to describe two sisters with congenital myasthenia associated with skeletal abnormalities and cataract. Case Reports Case 1 is a 13-year-old girl, whose younger sister is similarly affected (Case 2). The parents are well, and not consanguineous. She had bilateral ptosis from birth. The parents consulted a pediatrician when she was 1 year and 8 months, and a diagnosis of myasthenia gravis was made with the Tensilon test. She was floppy, and started to walk at the age of 6 years. She showed chest deformity since birth, and scoliosis was noted at the age of 7 years. Case 2 is 7-year-old. She also had bilateral ptosis from birth, and had measles encephalitis at the age of 6 months. She was also floppy and started to walk at the age of 3 years and 6 months. Examination They showed bilateral ptosis, a high arched palate, chest deformity, and scoliosis. There was weakness of the proximal muscles. There was no clinical improvement of ptosis after Tensilon injection. But repetitive ulnar nerve stimulation at a rate of 5 per second showed progressive diminution of the amplitude. This effect was reversed by intravenous Tensilon. Anti-acetylcholine receptor antibodies were not detected in either case. Histological studies of biopsied muscle (Case I: Quadriceps femoris, Case 2: Biceps brachii) showed mild variation in fiber size with normal fiber type distribution. There was punctated cataract in both cases. The IQ was 91 in the older sister, and 45 in the younger one. This familial incidence suggests an autosomal recessive heredity. Key words: Congenital myasthenia, skeletal abnormalities, cataract.