Heterogeneity of Classic Congenital Muscular Dystrophy With Involvement of the Central Nervous System: Report of Five Atypical Cases

Abstract

A heterogeneous group of patients with congenital muscular dystrophy associated with clinical or radiologic central nervous system involvement other than the severe classic form with merosin deficiency, muscle-eye-brain disease, and Walker-Warburg syndrome is described. A probable hereditary or familial occurrence could be suggested in all patients. One merosin-positive patient presented severe motor incapacity and cerebral atrophy without any clinical manifestation of central nervous system involvement. A second patient, also merosin-positive, had moderate motor and mental handicap, and epilepsy with no changes in neuroimaging. A third patient, found to have partial merosin deficiency by muscle biopsy, manifested severe psychomotor retardation and cerebral atrophy with foci of abnormal white-matter signal on magnetic resonance imaging. Finally, two merosin-positive siblings with microcephaly, mental retardation, and an incapacitating progressive neuromuscular course, exhibited cataracts without defects of neuronal migration or brain malformation. This report emphasizes the broad clinical spectrum and heterogeneity of merosin-positive congenital muscular dystrophy with associated central nervous system involvement, and illustrates the importance of further studies on clinical, immunohistochemical, and genetic grounds for identifying new subsets of congenital muscular dystrophy.

Neuropathologic Findings in a Child with a Novel Variant of TBCK-Related Encephaloneuronopathy

“…Given their relatively mature cytological features, most likely the presence of abundant white matter neurons reflected consequences of impaired migration during in utero development. [7][8][9] Similarly, the presence of multiple cavernous angiomas is considered a congenital anomaly in the CNS. 10,11 TBCK is a conserved protein kinase that associates with the mitotic apparatus and promotes cell growth, proliferation and F-actin cytoskeleton organization.…”

Axonal involvement with white matter abnormalities in merosin-positive congenital muscular dystrophy: A new association

“…Though unusual, CNS abnormalities do occur in this subtype. Recently, neurological abnormalities like microcephaly, mental retardation, epilepsy and white matter lucencies or changes resembling leukoencephalopathy, polymicrogyria, hypoplasia of the cerebellum or pons, cerebellar cysts and dilatation of ventricles have been described in association with MP CMD [10][11][12][13][14]. The intellectual handicap varies from mild to severe mental retardation.…”

“…There is no correlation between degree of intellectual impairment and neuroimaging abnormalities [10,13]. Some cases with epilepsy and mental retardation have normal scans [11]. Similarly, there is no correlation between the severity of muscle disease and presence of CNS symptoms or imaging abnormalities [8,11].…”

“…Some cases with epilepsy and mental retardation have normal scans [11]. Similarly, there is no correlation between the severity of muscle disease and presence of CNS symptoms or imaging abnormalities [8,11]. Other forms of CMD include rigid spine syndrome due to mutations in the gene encoding selenoprotein (SEPN 1) [15].…”

Doenças neuromusculares

“…Uma parte dos pacientes merosina-positiva apresenta manifestações clínicas ou neurorradiológicas, sugerindo comprometimento associado do SNC 25 : deficiência mental em 10%; epilepsia em 25%; alterações neurorradioló-gicas, tais como atrofia cortical, alteração da substância branca cerebral, como nas crianças merosina-negativa, hipoplasia cerebelar e displasia cortical fora do contexto da lissencefalia tipo II.…”