Broader clinical spectrum of Fukuyama-type congenital muscular dystrophy manifested by haplotype analysis

Fukuyama-type congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease are clinically similar autosomal-recessive diseases, characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. The classification of these disorders remains controversial. We analyzed five patients with congenital muscular dystrophy from four families who had severe eye and brain anomalies, such as retinal dysplasia and hydrocephalus, using polymorphic microsatellite markers flanking the Fukuyama-type congenital muscular dystrophy locus on chromosome 9q31. All patients were heterozygous for the Fukuyama muscular dystrophy founder haplotype with 3-kb insertion. In three cases, the other chromosome without the 3-kb insertion exhibited the same haplotype with a nonsense mutation on exon 3 of the Fukuyama gene. Thus, these three patients were compound heterozygotes for the condition. Severe eye anomalies such as retinal dysplasia or detachment and hydrocephalus could be included in the clinical spectrum of Fukuyama muscular dystrophy. The clinical spectrum of this disease is much broader than previously presumed.