G.P.318
Fukuyama congenital muscular dystrophy (FCMD), among the most common autosomal recessive disorders in the Japanese population, is characterized by congenital muscular dystrophy and brain malformations. It is essentially limited to Japan, and three-quarters of Japanese patients have a similar haplotype due to the ancestral founder mutation, a 3-kb retrotransposal insertion in the fukutin gene. Patient phenotypes can be classified as mild, typical, and severe depending on peak motor function. The typical form patients can sit without support or slide on the buttocks and account for 75% of FCMD cases. The patients who can crawl or walk are classified as having mild form and those lacking head control as having severe form. The rate of heterozygosity for the ancestral founder mutation was reported to be significantly higher in severe cases. Since the natural history of FCMD was reported long ago, we aimed to reevaluate the natural history of our FCMD patients. We retrospectively studied the medical records in 73 genetically diagnosed FCMD patients followed at our University from 1995. Forty-four patients were homozygous for the ancestral founder mutation and 24 had a compound heterozygous mutation. In the homozygous group, 28 patients were classified as typical form and 8 as mild form. In the heterozygous group, 13 patients had typical form and 8 had severe form. Head control and sitting without support were achieved, on average, at 7.6 months (m) and 14.6 m of age, respectively, in the homozygous group, but at 16.5 m and 39.1 m in the heterozygous group. Head control and sitting on average for each phenotype were: (i) 4.5 m/9 m in the walking, (ii)7.4 m/17.7 m in the sliding on the buttocks (iii) 10.5 m/21.3 m in sitting without support, and (iv) 21.7 m/- in the severe groups only with head control. Motor function deterioration started at 7.6 years, on average. Detailed assessment of motor development patterns for each FCMD phenotype may facilitate conducting clinical trials.