Secretory Diarrhea, Myopathy, And Deafness

Levy et al. (2003) described 3 sibs, a boy and 2 girls, with congenital myopathy, bullous eruption of the skin, secretory diarrhea, apparent zinc deficiency, failure to thrive, deafness, and microcephaly. The joint contractures resolved with age. Cryptorchidism was present in the male, and congenital heart disease was present in 1 of the 3 sibs. Myopathy improved with age and the blistering disappeared in the neonatal period without recurrence. The parents, of Italian ancestry, were not consanguineous and there were no other affected relatives. The disorder was thought to be autosomal recessive.

The syndrome in the sibs reported by Levy et al. (2003) appeared to be distinct from known syndromes of secretory diarrhea, myopathy, deafness, microcephaly, and zinc deficiency. Linkage analysis performed on DNA from the patients and their parents showed no linkage to markers on chromosome 12p12 flanking the GUCY2C gene (601330), which is a candidate gene for secretory diarrhea; to markers on chromosome 7q22-q31.1 flanking the DRA gene (126650), which is mutated in a form of secretory diarrhea (214700); or to markers on chromosome 15q22-qter flanking the MPI gene (154550), which is mutated in type Ib carbohydrate-deficient glycoprotein syndrome (602579). Because of the association of myopathy and blistering skin lesions in the sibs they reported, Levy et al. (2003) considered a recessive form of congenital muscular dystrophy in epidermolysis bullosa simplex (226670), which is caused by mutations in the PLEC1 gene (PLEC1; 601282). They excluded this disorder because of lack of histopathologic evidence for epidermolysis bullosa and the absence of PLEC1 gene mutations in 1 of the patients. Moreover, secretory diarrhea had not been reported in the epidermolysis bullosa-muscular dystrophy syndrome, and the myopathy in the patients reported by Levy et al. (2003) tended to improve with age rather than progress, as in epidermolysis bullosa-muscular dystrophy.