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Congenital muscular dystrophy of a non-fukuyama type with white matter hyperlucency on CT scan
Congenital Muscular Dystrophy of a Non-Fukuyama Type with White Matter Hyperlucency on CT Scan Ko-Pei Kao, MD and Kon-Pin Lin, MD
The term "congenital muscular dystrophy (CMD) " is used for a group of diseases with heterogeneous clinical and cranial CT scan manifestations. Recently, a distinct subtype, characterized by white matter hyperlucency on CT scan but normal or nearly normal intellectual junction, has been recognized in Western peoples and has even been named "occidental-type cerebromuscular dystrophy. " Here, we described two Chinese siblings with this type of CMD. Key words: Congenital muscular dystrophy, non-Fukuyama type, cranial cr, central nervous system involvement. Kao K-P, Lin K-P. Congenital muscular dystrophy of a non-Fukuyama type with white matter hyperlucency on CT scan. Brain Dev 1992;14:420-2
The term "congenital muscular dystrophy (CMD)" has been used for more than fifty years. Its heterogeneous clinical and cranial CT scan manifestations always make classification and nosologic status controversial. Recently, a distinct subtype of CMD, associated with white matter hyperlucency on CT scan but normal or nearly normal intellectual function, has been recognized in Western peoples and named "occidental-type cerebromuscular dystrophy (OCMD)" [1, 2]. However, only one Asian case of CMD with these features has been reported formally, from Japan [3]. Here, we describe two additional Chinese sibling cases. CASE REPORT The patients, a girl and a boy, were two of three siblings born to non-consanguineous healthy parents whose families have been residing in Taiwan for many generations. There is no family history of neuromuscular or mental illness. The other sister, 18 years old, is normal. Both cases had similar clinical presentations and courses. Pregnancy and delivery were normal except for poor fetal movement. Floppiness and diffuse proximal weakness were noted since birth, with bilateral equinovarus in the girl. Both cried, sucked weakly and experienced several
From the Neurological Institute, Veterans General Hospital, Taipei, Taiwan. Received for publication: July 22, 1992. Accepted for publication: September 5,1992. Correspondence address: Dr. Ko-pei Kao, Neurological Institute, Veterans General Hospital, Shi-pai, Taipei, Taiwan, ROC.
episodes of critical respiratory infection. They could never raise their heads in either prone or supine position. They could not crawl, and were always confmed to a wheel-chair or bed until death, with progressive spinal deformity and flexion contractures of the shoulders, elbows, hips, knees and ankles from the age of one. They could sit unaided from twenty months and four years of age, respectively. Speech, toilet training, and social and intellectual development were normal. Without any training or education, they could use two local languages normally and one foreign language partially, and were able to read simple books. They never suffered from convulsion or episodic mental lapse. They never had a noticeable enlargement on their calves. Physical examinations of the girl and the boy at six and five years of age (Fig 1) respectively, revealed long, thin and weak facies. Their heads were relatively large compared to their extremely thin bodies. Ocular movements were full with normal vision and fundi. Hearing was normal. Both patients had high-arched soft palates. Muscle weakness and wasting were diffuse and severe with only feeble movement of the forearms, hands and feet. Deep tendon reflexes were all unelicitable with flexor plantar response. Sensation was intact to all modalities. Serum pyruvate, and lactate were normal. Creatine kinase was normal in the girl but 151 units/L (normal < 120) in the boy. In both siblings, brain stem auditory and somatic sensory evoked potentials on bilateral median nerves were unremarkable. EMG showed generalized myopathic potentials. CT scans of the head (Fig 2) in both the girl at 6 and the boy at 5 showed similar symmetrical diffuse white matter hyperlucency in the cerebrum without pachygyria, polymicrogyria, lissencephaly, hydrocephalus
or cortical atrophy. In the boy, a repeat CT scan two years later revealed no change. In the girl, muscle biopsy showed far advanced dystrophic changes (Fig 3). The EEG result was normal in the boy but showed excessive fast activity in the girl. Neither had slow wave or spike activity. Intellectual functions evaluated with the BinetSimon scale were 93 and 99, respectivel (normal range: 90-109).
Fig 1 Physical appearance of the girl at six and the boy at [we years of age showing their long, thin and weak faces, defonnity of the spine and flexion contractures of the shoulders, elbows, hips and ankles.
Both patients suffered from deteriorating weakness and wasting, with death due to pneumon;tic respiratory failure occurring at eleven and nine years of age in the girl and the boy, respectively. No autopsy was obtainable.
DISCUSSION The clinical and myopathological presentations of these
Fig 2 CT scan of the head of the boy at jive years of age, showing diffuse hyperlucency in the white matter of the cerebrum.
Fig 3 Muscle biopsy (left biceps) on the girl at six years of age, showing severe replacement of fatty and fibrotic tissues with some scattered roud fibers varying in size.
Kao and Lin: Non-Fukuyama CMD in Taiwan 421
two Chinese siblings, a girl and a boy, are consistent with CMD. However, the lack of clinical and EEG seizure disorder, and the normal intellectual functions seem to constitute a form different from typical or atypical Fukuyama type CMD (FCMD) [4,5], which has been reported mainly in Japanese. The diffuse white matter hyperlucency observed on the CT scans also can be seen in FCMD, particularly between one and two years of age [6] ; however, in FCMD, it is frequently associated with ventricular dilatation, cortical atrophy [7] or other dysplastic changes. In addition, in most cases of FCMD this hyperlucency decreased or became normalized at 2 or 3 years of age [6, 7] and it is considered that a delay of myelination is responsible [6]. In our cases, the white matter hyperlucency was not associated with other changes and persisted after two years; these findings are not in agreement with those observed in FCMD. Recently, CMD with white matter hyperlucency as the major finding on cranial CT scan and normal or nearly normal mental development has been recognized as an intermediate form between FCMD and pure form of CMD. As this form of CMD appears to be more prevalent in Western peoples [1, 2, 8-10] , the term "occidental-type cerebromuscular dystrophy" has recently been applied by some authors [1, 2, 9] . However, our cases certainly share all the features of this form of CMD, which had been reported in Japan in one case formally [3] and a few others as a CMD type II [4,5]. Assuredly, none of these cases should be categorized as FCMD. The cranial CT scan changes are not solely in the form of white matter hyperlucency in this intermediate type of CMD. They may also manifest varying degrees of cortical atrophy and ventricular dilatation [1, 8, 9]. The distinction between this form of CMD and FCMD appears not to be clear-cut, either clinically or radiologically [1, 8, 10], but the increasing utilization of CT scans or MRI in CMD cases will definitely increase the identification of the intermediate type of CMD. Importantly, the presentation of our cases in two Chinese siblings renders it inappropriate to name this type of CMD "occidental-type cerebromuscular dystrophy." Further CNS pathological and genetic
422 Brain & Development, Vol 14, No 6, 1992
studies on variable forms of CMD on the basis of international cooperation are necessary for setting classification issues within CMD nosology.
ACKNOWLEDGMENTS This work is supported partially by grant (DOH82-TD-Q85) from NIH (Taiwan, ROC). We thank Dr. Emil W. Chynn for his assistance in the preparation of the manuscript.
REFERENCES 1. Topaloglu H, Yalaz K, Renda Y, et al. Occidental type cerebromuscular dystrophy: a report of eleven cases. J Neurol Neurosurg Psychiatry 1991;54: 226-9. 2. Castro-Gago M, Pena-Guitian J. Congenital muscular dystrophy of a non-Fukuyama type with characteristic CT images. Brain Dev (Tokyo) 1988;10: 60. 3. Yoshioka M, Kuroki S, Mizue H. Congenital muscular dystrophy of non-Fukuyama type with characteristic CT images. Brain Dev (Tokyo) 1987;9: 316-8. 4. Fukuyama Y, Osawa M, Suzuki H. Congenital progressive muscular dystrophy of the Fukuyama type-clinical, genetic and pathological considerations. Brain Dev (Tokyo) 1981;3: 1-29. _ 5. Osawa M, Arai Y, Ikenaka H, et al. Fukuyama type congenital progressive muscular dystrophy. Acta Paediatr Jpn (Tokyo) 1991;33:261-9. 6. Yoshioka M, Saiwai S. Congenital muscular dystrophy (Fukuyama type)-changes in the white matter lower density on CT. Brain Dev (Tokyo) 1988;10:41-4. 7. Yoshioka M, Okuno T, Ito M, Konishi Y, Itagaki Y, Sakamoto Y. Congenital muscular dystrophy (Fukuyama type): repeated CT studies in 19 children. Cornput Tornogr 1981;5: 81-8. 8. Trevisan CP, Carollo C, Segalla P, Angelini C, Drigo P, Giordano R. Congenital muscular dystrophy: brain alterations in an unselected series of Western patients. J Neurol Neurosurg Psychiatry 1991;54: 330-4. 9. Topaloglu H, Yalaz K, Kale G, Ergin M. Congenital muscular dystrophy with cerebral involvement-report of a case of "occidental type cerebromuscular dystrophy"? Neuropediatrics 1990;21: 53-4. 10. Topaloglu H, Yalaz K, Renda Y, Kale G, Caglar M, Gogus S. Congenital muscular dystrophy (non-Fukuyama type) in Turkey: a clinical and pathological evaluation. Brain Dev (Tokyo) 1989; 11: 341-4.
The term "congenital muscular dystrophy (CMD) " is used for a group of diseases with heterogeneous clinical and cranial CT scan manifestations. Recently, a distinct subtype, characterized by white matter hyperlucency on CT scan but normal or nearly normal intellectual junction, has been recognized in Western peoples and has even been named "occidental-type cerebromuscular dystrophy. " Here, we described two Chinese siblings with this type of CMD. Key words: Congenital muscular dystrophy, non-Fukuyama type, cranial cr, central nervous system involvement. Kao K-P, Lin K-P. Congenital muscular dystrophy of a non-Fukuyama type with white matter hyperlucency on CT scan. Brain Dev 1992;14:420-2
The term "congenital muscular dystrophy (CMD)" has been used for more than fifty years. Its heterogeneous clinical and cranial CT scan manifestations always make classification and nosologic status controversial. Recently, a distinct subtype of CMD, associated with white matter hyperlucency on CT scan but normal or nearly normal intellectual function, has been recognized in Western peoples and named "occidental-type cerebromuscular dystrophy (OCMD)" [1, 2]. However, only one Asian case of CMD with these features has been reported formally, from Japan [3]. Here, we describe two additional Chinese sibling cases. CASE REPORT The patients, a girl and a boy, were two of three siblings born to non-consanguineous healthy parents whose families have been residing in Taiwan for many generations. There is no family history of neuromuscular or mental illness. The other sister, 18 years old, is normal. Both cases had similar clinical presentations and courses. Pregnancy and delivery were normal except for poor fetal movement. Floppiness and diffuse proximal weakness were noted since birth, with bilateral equinovarus in the girl. Both cried, sucked weakly and experienced several
From the Neurological Institute, Veterans General Hospital, Taipei, Taiwan. Received for publication: July 22, 1992. Accepted for publication: September 5,1992. Correspondence address: Dr. Ko-pei Kao, Neurological Institute, Veterans General Hospital, Shi-pai, Taipei, Taiwan, ROC.
episodes of critical respiratory infection. They could never raise their heads in either prone or supine position. They could not crawl, and were always confmed to a wheel-chair or bed until death, with progressive spinal deformity and flexion contractures of the shoulders, elbows, hips, knees and ankles from the age of one. They could sit unaided from twenty months and four years of age, respectively. Speech, toilet training, and social and intellectual development were normal. Without any training or education, they could use two local languages normally and one foreign language partially, and were able to read simple books. They never suffered from convulsion or episodic mental lapse. They never had a noticeable enlargement on their calves. Physical examinations of the girl and the boy at six and five years of age (Fig 1) respectively, revealed long, thin and weak facies. Their heads were relatively large compared to their extremely thin bodies. Ocular movements were full with normal vision and fundi. Hearing was normal. Both patients had high-arched soft palates. Muscle weakness and wasting were diffuse and severe with only feeble movement of the forearms, hands and feet. Deep tendon reflexes were all unelicitable with flexor plantar response. Sensation was intact to all modalities. Serum pyruvate, and lactate were normal. Creatine kinase was normal in the girl but 151 units/L (normal < 120) in the boy. In both siblings, brain stem auditory and somatic sensory evoked potentials on bilateral median nerves were unremarkable. EMG showed generalized myopathic potentials. CT scans of the head (Fig 2) in both the girl at 6 and the boy at 5 showed similar symmetrical diffuse white matter hyperlucency in the cerebrum without pachygyria, polymicrogyria, lissencephaly, hydrocephalus
or cortical atrophy. In the boy, a repeat CT scan two years later revealed no change. In the girl, muscle biopsy showed far advanced dystrophic changes (Fig 3). The EEG result was normal in the boy but showed excessive fast activity in the girl. Neither had slow wave or spike activity. Intellectual functions evaluated with the BinetSimon scale were 93 and 99, respectivel (normal range: 90-109).
Fig 1 Physical appearance of the girl at six and the boy at [we years of age showing their long, thin and weak faces, defonnity of the spine and flexion contractures of the shoulders, elbows, hips and ankles.
Both patients suffered from deteriorating weakness and wasting, with death due to pneumon;tic respiratory failure occurring at eleven and nine years of age in the girl and the boy, respectively. No autopsy was obtainable.
DISCUSSION The clinical and myopathological presentations of these
Fig 2 CT scan of the head of the boy at jive years of age, showing diffuse hyperlucency in the white matter of the cerebrum.
Fig 3 Muscle biopsy (left biceps) on the girl at six years of age, showing severe replacement of fatty and fibrotic tissues with some scattered roud fibers varying in size.
Kao and Lin: Non-Fukuyama CMD in Taiwan 421
two Chinese siblings, a girl and a boy, are consistent with CMD. However, the lack of clinical and EEG seizure disorder, and the normal intellectual functions seem to constitute a form different from typical or atypical Fukuyama type CMD (FCMD) [4,5], which has been reported mainly in Japanese. The diffuse white matter hyperlucency observed on the CT scans also can be seen in FCMD, particularly between one and two years of age [6] ; however, in FCMD, it is frequently associated with ventricular dilatation, cortical atrophy [7] or other dysplastic changes. In addition, in most cases of FCMD this hyperlucency decreased or became normalized at 2 or 3 years of age [6, 7] and it is considered that a delay of myelination is responsible [6]. In our cases, the white matter hyperlucency was not associated with other changes and persisted after two years; these findings are not in agreement with those observed in FCMD. Recently, CMD with white matter hyperlucency as the major finding on cranial CT scan and normal or nearly normal mental development has been recognized as an intermediate form between FCMD and pure form of CMD. As this form of CMD appears to be more prevalent in Western peoples [1, 2, 8-10] , the term "occidental-type cerebromuscular dystrophy" has recently been applied by some authors [1, 2, 9] . However, our cases certainly share all the features of this form of CMD, which had been reported in Japan in one case formally [3] and a few others as a CMD type II [4,5]. Assuredly, none of these cases should be categorized as FCMD. The cranial CT scan changes are not solely in the form of white matter hyperlucency in this intermediate type of CMD. They may also manifest varying degrees of cortical atrophy and ventricular dilatation [1, 8, 9]. The distinction between this form of CMD and FCMD appears not to be clear-cut, either clinically or radiologically [1, 8, 10], but the increasing utilization of CT scans or MRI in CMD cases will definitely increase the identification of the intermediate type of CMD. Importantly, the presentation of our cases in two Chinese siblings renders it inappropriate to name this type of CMD "occidental-type cerebromuscular dystrophy." Further CNS pathological and genetic
422 Brain & Development, Vol 14, No 6, 1992
studies on variable forms of CMD on the basis of international cooperation are necessary for setting classification issues within CMD nosology.
ACKNOWLEDGMENTS This work is supported partially by grant (DOH82-TD-Q85) from NIH (Taiwan, ROC). We thank Dr. Emil W. Chynn for his assistance in the preparation of the manuscript.
REFERENCES 1. Topaloglu H, Yalaz K, Renda Y, et al. Occidental type cerebromuscular dystrophy: a report of eleven cases. J Neurol Neurosurg Psychiatry 1991;54: 226-9. 2. Castro-Gago M, Pena-Guitian J. Congenital muscular dystrophy of a non-Fukuyama type with characteristic CT images. Brain Dev (Tokyo) 1988;10: 60. 3. Yoshioka M, Kuroki S, Mizue H. Congenital muscular dystrophy of non-Fukuyama type with characteristic CT images. Brain Dev (Tokyo) 1987;9: 316-8. 4. Fukuyama Y, Osawa M, Suzuki H. Congenital progressive muscular dystrophy of the Fukuyama type-clinical, genetic and pathological considerations. Brain Dev (Tokyo) 1981;3: 1-29. _ 5. Osawa M, Arai Y, Ikenaka H, et al. Fukuyama type congenital progressive muscular dystrophy. Acta Paediatr Jpn (Tokyo) 1991;33:261-9. 6. Yoshioka M, Saiwai S. Congenital muscular dystrophy (Fukuyama type)-changes in the white matter lower density on CT. Brain Dev (Tokyo) 1988;10:41-4. 7. Yoshioka M, Okuno T, Ito M, Konishi Y, Itagaki Y, Sakamoto Y. Congenital muscular dystrophy (Fukuyama type): repeated CT studies in 19 children. Cornput Tornogr 1981;5: 81-8. 8. Trevisan CP, Carollo C, Segalla P, Angelini C, Drigo P, Giordano R. Congenital muscular dystrophy: brain alterations in an unselected series of Western patients. J Neurol Neurosurg Psychiatry 1991;54: 330-4. 9. Topaloglu H, Yalaz K, Kale G, Ergin M. Congenital muscular dystrophy with cerebral involvement-report of a case of "occidental type cerebromuscular dystrophy"? Neuropediatrics 1990;21: 53-4. 10. Topaloglu H, Yalaz K, Renda Y, Kale G, Caglar M, Gogus S. Congenital muscular dystrophy (non-Fukuyama type) in Turkey: a clinical and pathological evaluation. Brain Dev (Tokyo) 1989; 11: 341-4.