Myelocystocele-cloacal exstrophy in a pedigree with a mitochondrial 12S rRNA mutation, aminoglycoside-induced deafness, pigmentary disturbances, and spinal anomalies

A large Filipino-American family with progressive matrilineal hearing loss, premature graying, depigmented patches, and digital anomalies was ascertai ned through a survey of a spina bifida clinic for neural crest disorders. D eafness followed a matrilineal pattern of inheritance and was associated wi th the A1555G mutation in the 12S rRNA gene (MTRNR1) in affected individual s as well as unaffected maternal relatives. Several other malformations wer e found in carriers of the mutation. The proband had a myelocystocele, Arno ld-Chiari type I malformation, cloacal exstrophy, and severe early-onset he aring loss. Several family members had premature graying, white forelock, c ongenital leukoderma with or without telecanthus, somewhat suggestive of a Waardenburg syndrome variant. In addition to the patient with myelocystocel e, two individuals had scoliosis and one had segmentation defects of spinal vertebrae. The syndromic characteristics reported here are novel for the m itochondrial A1555G substitution, and may result from dysfunction of mitoch ondrial genes during early development. However, the mitochondrial A1555G m utation is only rarely associated with neural tube defects as it was not fo und in a screen of 218 additional individuals with spina bifida, four of wh om had congenital hearing loss. (C) 2000 Wiley-Liss, Inc.