Clinical spectrum and genetic studies of Fukuyama congenital muscular dystrophy

Abstract

The association of congenital muscular dystrophy (CMD) with type II lissencephaly and ocular anomalies is found in Fukuyama CMD (FCMD), the Walker-Warburg syndrome (WWS), and muscle-eye-brain disease (MEBD). The classification of these disorders remains controversial. Between 1972 and 1992, we performed clinical and genetic studies in 41 families of FCMD, which is particularly frequent in Japan. Nine families (22%) had multiple affected children ("familial" FCMD). The other 32 families had only one affected child ("sporadic" FCMD). Parental consanguinity was documented in 5 sporadic FCMD families and in none of the familial cases. In total, 48 patients, including 7 sib pairs, were evaluated with regard to maximum motor ability, mental and convulsion states, cranial CT or MRI findings, and EEG and ophthalmological data. A difference between the sibs in motor ability was apparent in 4 families. Mental status also showed wide variation. Two of 7 sib pairs differed in EEG findings. The familial FCMD patients showed relatively more severe motor disability than that in the sporadic FCMD patients, while in mental and convulsion states no significant difference was found in both groups. Interestingly, in one family hydrocephalus was found in only one of the sibs. In addition, this patient showed encephalocele and retinal detachment at birth. Based on these observations, we consider the clinical spectrum of FCMD to be much broader than previously described and to overlap with that of "mild" WWS and MEBD.