53
Congenital Muscular Dystrophy with Cerebral Involvement Report of a Case of "Oeeidental Type Cerebromuscular Dystrophy"? By H. Topaloglu 1, K. Yalaz 1, G. Kale2 and M. Ergin1
Abstract Cerebral CT scan abnormalities have been seen to be afflicted with some cases of classic occidental type congenital muscular dystrophy (CMD) with normal or borderline intelligence without neurological abnormality. A case is presented with early hypotonia, joint contractures, museIe biopsy features of CMD, normal intelligence and diffuse white matter hyperlucency on CT scan. Every CMD case should be screened with cerebral CT and magnetic resonance (MRI) scans to reach more aspects of this heterogenous disorder. Keywords Congenital muscular dystrophy - Normal mental development - White matter involvement
Introduclion Congenital muscular dystrophy (CMD) is a heterogenous group of disorders with varying clinical presentations and pathological features. We are now ahle to distinguish four separate entities within CMD nosology. Typical CMD with normal or subnormal intelligence, Fukuyama's CMD (FCMD), the cerebro-ocular dysplasia-muscular dystrophy syndrome and same forms which hardly fit to any category (3, 5, 7, 9). An intermediate form between classic occidental-typical type CMD and FCMD with early hypotonia, preserved intelligence and white matter hypodensity on CT scan has recently been suggested to be named as "occidental-type cerebromuscular dystrophy", because this form appears to be prevalent in the west (2). We report a similar case of CMD observed in a Turkish boy.
and joint contractures present since birth. He was the second child of a non-consanguineous couple. A 6-year-old female sibling is healthy. Pregnancy was uneventful with normal intrauterine movements. He was born at term with a birthweight of 2,950 g. Bilateral ankle contractures were noted at birth. There were no problems other than hypotonia and muscular weakness at the neonatal period. His motor development was delayed; he held his neck at 7 months, sat without support barely at 12 months. Contracture of the right wrist was observed at 7 months. Physical examination on admission showed evidence of undernourishment and marked hypotonia. His weight was 7,150 g (below 5th centile); length 75 cm (30th centile); head circumference 46.5 cm (30th centile). His facial appearence was mask like. Ocular movements were full and fundi were normal. Findings from examination of the ehest and abdomen were unremarkable. There were flexion contractures at the right wrist and both ankles. Quadriceps museIes were slightly enlarged. Tendon reflexes were absent. Marked scoliosis was noted. He was unable to stand erect without support. His mental developmental quotient was normal. Serum creatine kinase was elevated at 1514 u/L (N. 20-191). EMG showed polyphasie potentials of low amplitude and brief duration. X-ray of the hips did not show any evidence of dislocation. A CT scan of the head showed cortical atrophy and marked hyperlucency of the white matter and ventricular dilation (Fig. 1). EEG was normal. A biopsy from the gastrocnemius museIe showed variation in fiber size and moderate fibrous tissue infiltration along with mild fat replacement (Fig. 2). On the basis of these findings we made a diagnosis of CMD.
Case report A 12-month-old Turkish male infant from Southern part of Turkey was evaluated because of hypotonia
Received April 20, 1989; accepted lune 9, 1989 Neuropediatrics 21 (1990) 53-54 © Hippokrates Verlag Stuttgart
Fig. 1
cr scan. Cortical atrophy, marked white matter hyperlucency.
Downloaded by: NYU. Copyrighted material.
Departments of Ipediatric Neurology and 2pathology, Hacettepe University Children's Hospital, Ankara, Turkey
Neuropediatries 21 (1990)
H. Topaloglu et al
Existence of various forms of CMD is very likely associated with more or less marked disorders in cerebra! organogenesis (5, 11). It is possible that a defect in closely linked genes or in a single gene with pleiotrophic effect could be responsible for the muscular dystrophy, cerebral malformation and white matter involvement (6).
Fig. 2 Museie biopsy. Variation in fiber size, moderate fibrosis, mild adiposis, scattered degenerating fibers. HE x 200.
We propose that, since pathology is not COllfined solely to muscle and membranes in this group of disorders, every CMD patient regardless of the mental status should be screened with cerebral CT and magnetic resonance (MRI) scans. Also, extensive morphological examination is mandatory and autopsy studies should be done wherever possible. These and the aid of molecular genetic studies will enable us to recognize more aspects of CMD and help settling classification issues within CMD nosology.
References Discussion In the majority of cases with CMD, intelligence is normal or borderline, so central nervous system is generally considered to be unaffected (9). In some cases of classic occidental type with normal intelligence, cerebral CT scan abnormalities have been observed (5, 6, 8, 10). This finding shows a considerable amount of overlapping in clinical presentations of CMD patients. These patients feature with amytrophy, involvement of the facial musculature, multiple joint contractures and some dysmorphic features; long and thin face, abnormalities of jaw articulations and high arched palate. Intelligence may be normal or slightly lowered. All these patients have a marked white matter hypodensity on CT scan (5). In the literature only one case was subjected to necropsy (6). Abnormalities consisted of degeneration of myelin sheath, cerebellar hypoplasia and cortical areas of micropolygyria, cerebral neural loss and heterotopic nerve cells. These patients constitute an original subgroup and different from the other forms of CMD (1). In this group of patients the scannographic white matter hyperlucency persists after several years (4), whereas in FCMD a normalisation is observed for which a delayed myelination processing is suspected to be responsible (12). White matter hyperlucency on CT scan is observed in various pathological conditions such as neuronal degeneration, leukodystrophies, lissencephaly and encephalitis (5). The group of CMD patients with cerebral involvement may be added to this list. For our patient we can not draw conclusions about the nature of the CT scan white matter hyperlucency, because we lack cerebral radio-anatomical correlations. In any case he fits into the recently classified "occidental-type cerebromuscular dystrophy" group with typical clinical features and CT scan abnormalities. CT scan was useful in our case especially for demonstration of the cerebral involvement. His mental development was normal, and otherwise we could not have documented it.
1
Castro-Gago, M., 1. Diaz-Cardama, L. Monasterio, M. Fuster, B. PerezBeeerra, ]. Pena: Congenital muscular dystrophy with central nenrous system involvement: an intermediate form? The Annals (Houston) 7
2
Castro-Gago, M.,]. Pena-Guitian: Congenital muscular dystrophy of a non-Fukuyama type with characteristic CT images (letter). Brain Dev. 10
(1985) 5
(1988) 60
Dambska, M., K. Wisniewski,]. Sher: Cerebro-oculo-muscular syndrome: A variant of Fukuyama congenital muscular dystrophy. Clin. Neuropathol. 25 (1982) 93 4 Behenne, B., M. Pages, C. Marty-Double: Congenital muscular dystrophy with cerebral white matter spongiosis. Brain Dev. 6 (1984) 491 5 Eehenne, B., M. Arthuis, C. Billard,]. Campos-Castello, Y. Castei, O. Dulae, D. Fontan, A. Gauthier, S. Kulakowski, G. De Meuron, ]. R. Moore, M. Nieto-Barrera, M. Pages, D. Parain, L. Pavone, G. Ponsot. Congenital muscular dystrophy and cerebral CT scan anomalies. Resulu of a collaborative study of the Societe de Neurologie Infantile. J. Neurol Sei. 75 (1986) 7 6 Egger,]., B. E. Kendall, M. Erdohazi, B. D. Lake,]. Wilson, E. M. Brett Involvement of the central nenrous system in congenital muscular dystro phies. Dev. Med. Child Neurol. 25 (1983) 32 7 Fukuyama, Y., M. Osawa, H. Suzuki: Congenital progressive dystroph~ of the Fukuyama type. Clinical, genetic and pathological considerations Brain Dev. 3 (1981) 1 8 Gobemado,]. M., A. Gimeno: Changes in cerebral white matter in twc cases of congenital muscular dystrophy. Pediatr. Radiol. 12 (1982) 201 9 MeMenamin,]. B., L. E. Beeker, E. G. Murphy: Congenital museula dystrophy: a clinicopathological report of 24 cases. J. Pediatr. 100 (1982 3
692 10
11 12
Nogen, A. G.: Congenital muscular disease and abnormal findings 0 computerized tomography. Dev. Med. Child Neurol. 22 (1980) 658 Samat, H. B.: Cerebral dysgenesis and their influence on fetal muscle dc velopment. Brain Dev. 8 (1986) 494 Yoshioka, M., S. Saiwai: Congenital muscular dystrophy (Fukuyarr type) - Changes in the white matter low density on CT. Brain Dev. 1 (1988) 41
Dr. H. Topaloglu Dept. of Pediatric Neurology Hacettepe Children's Hospital Ankara, Turkey
Downloaded by: NYU. Copyrighted material.
54
Congenital Muscular Dystrophy with Cerebral Involvement Report of a Case of "Oeeidental Type Cerebromuscular Dystrophy"? By H. Topaloglu 1, K. Yalaz 1, G. Kale2 and M. Ergin1
Abstract Cerebral CT scan abnormalities have been seen to be afflicted with some cases of classic occidental type congenital muscular dystrophy (CMD) with normal or borderline intelligence without neurological abnormality. A case is presented with early hypotonia, joint contractures, museIe biopsy features of CMD, normal intelligence and diffuse white matter hyperlucency on CT scan. Every CMD case should be screened with cerebral CT and magnetic resonance (MRI) scans to reach more aspects of this heterogenous disorder. Keywords Congenital muscular dystrophy - Normal mental development - White matter involvement
Introduclion Congenital muscular dystrophy (CMD) is a heterogenous group of disorders with varying clinical presentations and pathological features. We are now ahle to distinguish four separate entities within CMD nosology. Typical CMD with normal or subnormal intelligence, Fukuyama's CMD (FCMD), the cerebro-ocular dysplasia-muscular dystrophy syndrome and same forms which hardly fit to any category (3, 5, 7, 9). An intermediate form between classic occidental-typical type CMD and FCMD with early hypotonia, preserved intelligence and white matter hypodensity on CT scan has recently been suggested to be named as "occidental-type cerebromuscular dystrophy", because this form appears to be prevalent in the west (2). We report a similar case of CMD observed in a Turkish boy.
and joint contractures present since birth. He was the second child of a non-consanguineous couple. A 6-year-old female sibling is healthy. Pregnancy was uneventful with normal intrauterine movements. He was born at term with a birthweight of 2,950 g. Bilateral ankle contractures were noted at birth. There were no problems other than hypotonia and muscular weakness at the neonatal period. His motor development was delayed; he held his neck at 7 months, sat without support barely at 12 months. Contracture of the right wrist was observed at 7 months. Physical examination on admission showed evidence of undernourishment and marked hypotonia. His weight was 7,150 g (below 5th centile); length 75 cm (30th centile); head circumference 46.5 cm (30th centile). His facial appearence was mask like. Ocular movements were full and fundi were normal. Findings from examination of the ehest and abdomen were unremarkable. There were flexion contractures at the right wrist and both ankles. Quadriceps museIes were slightly enlarged. Tendon reflexes were absent. Marked scoliosis was noted. He was unable to stand erect without support. His mental developmental quotient was normal. Serum creatine kinase was elevated at 1514 u/L (N. 20-191). EMG showed polyphasie potentials of low amplitude and brief duration. X-ray of the hips did not show any evidence of dislocation. A CT scan of the head showed cortical atrophy and marked hyperlucency of the white matter and ventricular dilation (Fig. 1). EEG was normal. A biopsy from the gastrocnemius museIe showed variation in fiber size and moderate fibrous tissue infiltration along with mild fat replacement (Fig. 2). On the basis of these findings we made a diagnosis of CMD.
Case report A 12-month-old Turkish male infant from Southern part of Turkey was evaluated because of hypotonia
Received April 20, 1989; accepted lune 9, 1989 Neuropediatrics 21 (1990) 53-54 © Hippokrates Verlag Stuttgart
Fig. 1
cr scan. Cortical atrophy, marked white matter hyperlucency.
Downloaded by: NYU. Copyrighted material.
Departments of Ipediatric Neurology and 2pathology, Hacettepe University Children's Hospital, Ankara, Turkey
Neuropediatries 21 (1990)
H. Topaloglu et al
Existence of various forms of CMD is very likely associated with more or less marked disorders in cerebra! organogenesis (5, 11). It is possible that a defect in closely linked genes or in a single gene with pleiotrophic effect could be responsible for the muscular dystrophy, cerebral malformation and white matter involvement (6).
Fig. 2 Museie biopsy. Variation in fiber size, moderate fibrosis, mild adiposis, scattered degenerating fibers. HE x 200.
We propose that, since pathology is not COllfined solely to muscle and membranes in this group of disorders, every CMD patient regardless of the mental status should be screened with cerebral CT and magnetic resonance (MRI) scans. Also, extensive morphological examination is mandatory and autopsy studies should be done wherever possible. These and the aid of molecular genetic studies will enable us to recognize more aspects of CMD and help settling classification issues within CMD nosology.
References Discussion In the majority of cases with CMD, intelligence is normal or borderline, so central nervous system is generally considered to be unaffected (9). In some cases of classic occidental type with normal intelligence, cerebral CT scan abnormalities have been observed (5, 6, 8, 10). This finding shows a considerable amount of overlapping in clinical presentations of CMD patients. These patients feature with amytrophy, involvement of the facial musculature, multiple joint contractures and some dysmorphic features; long and thin face, abnormalities of jaw articulations and high arched palate. Intelligence may be normal or slightly lowered. All these patients have a marked white matter hypodensity on CT scan (5). In the literature only one case was subjected to necropsy (6). Abnormalities consisted of degeneration of myelin sheath, cerebellar hypoplasia and cortical areas of micropolygyria, cerebral neural loss and heterotopic nerve cells. These patients constitute an original subgroup and different from the other forms of CMD (1). In this group of patients the scannographic white matter hyperlucency persists after several years (4), whereas in FCMD a normalisation is observed for which a delayed myelination processing is suspected to be responsible (12). White matter hyperlucency on CT scan is observed in various pathological conditions such as neuronal degeneration, leukodystrophies, lissencephaly and encephalitis (5). The group of CMD patients with cerebral involvement may be added to this list. For our patient we can not draw conclusions about the nature of the CT scan white matter hyperlucency, because we lack cerebral radio-anatomical correlations. In any case he fits into the recently classified "occidental-type cerebromuscular dystrophy" group with typical clinical features and CT scan abnormalities. CT scan was useful in our case especially for demonstration of the cerebral involvement. His mental development was normal, and otherwise we could not have documented it.
1
Castro-Gago, M., 1. Diaz-Cardama, L. Monasterio, M. Fuster, B. PerezBeeerra, ]. Pena: Congenital muscular dystrophy with central nenrous system involvement: an intermediate form? The Annals (Houston) 7
2
Castro-Gago, M.,]. Pena-Guitian: Congenital muscular dystrophy of a non-Fukuyama type with characteristic CT images (letter). Brain Dev. 10
(1985) 5
(1988) 60
Dambska, M., K. Wisniewski,]. Sher: Cerebro-oculo-muscular syndrome: A variant of Fukuyama congenital muscular dystrophy. Clin. Neuropathol. 25 (1982) 93 4 Behenne, B., M. Pages, C. Marty-Double: Congenital muscular dystrophy with cerebral white matter spongiosis. Brain Dev. 6 (1984) 491 5 Eehenne, B., M. Arthuis, C. Billard,]. Campos-Castello, Y. Castei, O. Dulae, D. Fontan, A. Gauthier, S. Kulakowski, G. De Meuron, ]. R. Moore, M. Nieto-Barrera, M. Pages, D. Parain, L. Pavone, G. Ponsot. Congenital muscular dystrophy and cerebral CT scan anomalies. Resulu of a collaborative study of the Societe de Neurologie Infantile. J. Neurol Sei. 75 (1986) 7 6 Egger,]., B. E. Kendall, M. Erdohazi, B. D. Lake,]. Wilson, E. M. Brett Involvement of the central nenrous system in congenital muscular dystro phies. Dev. Med. Child Neurol. 25 (1983) 32 7 Fukuyama, Y., M. Osawa, H. Suzuki: Congenital progressive dystroph~ of the Fukuyama type. Clinical, genetic and pathological considerations Brain Dev. 3 (1981) 1 8 Gobemado,]. M., A. Gimeno: Changes in cerebral white matter in twc cases of congenital muscular dystrophy. Pediatr. Radiol. 12 (1982) 201 9 MeMenamin,]. B., L. E. Beeker, E. G. Murphy: Congenital museula dystrophy: a clinicopathological report of 24 cases. J. Pediatr. 100 (1982 3
692 10
11 12
Nogen, A. G.: Congenital muscular disease and abnormal findings 0 computerized tomography. Dev. Med. Child Neurol. 22 (1980) 658 Samat, H. B.: Cerebral dysgenesis and their influence on fetal muscle dc velopment. Brain Dev. 8 (1986) 494 Yoshioka, M., S. Saiwai: Congenital muscular dystrophy (Fukuyarr type) - Changes in the white matter low density on CT. Brain Dev. 1 (1988) 41
Dr. H. Topaloglu Dept. of Pediatric Neurology Hacettepe Children's Hospital Ankara, Turkey
Downloaded by: NYU. Copyrighted material.
54
