Myotubular Myopathy With Abnormal Genital Development

A number sign (#) is used with this entry because of the likelihood that this disorder represents a contiguous gene syndrome.

Clinical Features

In the course of screening 38 patients with myotubular myopathy for interstitial deletions at Xq28, Hu et al. (1996) found 2 unrelated males in whom deletion was associated not only with MTM1 but also with abnormal genital development. One male had a micropenis and bifid scrotum without palpable testes. An introitus vagina was present and genitography showed a vaginal pouch of 2 to 3 cm. He was initially considered female. The second boy showed perineoscrotal hypospadias.

Bartsch et al. (1999) studied a family in which 2 male infants, both deceased, had myotubular myopathy and intersexual genitalia.

Cytogenetics

Hu et al. (1996) suggested that the presence of abnormal genital development in their patients in addition to myotubular myopathy were best explained by a contiguous gene syndrome. The deletion defined a 430-kb region that contains the MTM1 gene and most likely a gene implicated in male sexual development.

Laporte et al. (1997) isolated a novel human gene that was entirely deleted in the 2 boys reported by Hu et al. (1996). The gene, F18 (CXORF6; 300120), was located in proximal Xq28, approximately 80 kb centromeric to MTM1. F18 was thus a strong candidate for implication in the intersexual genitalia present in the 2 boys and/or for other disorders that map to proximal Xq28.

Using FISH in the mother of 2 male infants with myotubular myopathy and intersexual genitalia, Bartsch et al. (1999) detected a hemizygous deletion including the MTM1 gene and F18. DNA studies with short tandem repeats as markers, within and flanking the deleted segment, confirmed the deletion in the family and were used for prenatal diagnosis. The findings confirmed the existence of this novel contiguous gene syndrome and supported the possibility that deletion of F18 or a neighboring gene may cause ambiguous genitalia or severe hypospadias in males. The mother had low muscle power and marked menstrual irregularities which may indicate that she is a manifesting carrier and that the deletion may include a gene (F18 or other) for gonadal function in females.