Myotubular Myopathy with Abnormal Genital Development

Myotubular myopathies (also called centronuclear myopathies) are inherited neuromuscular disorders. The most severe form is called X-linked recessive myotubular myopathy (XLMTM) which is typically present at birth and characterized by muscle weakness, hypotonia, and respiratory failure (Pierson et al. 2005). In 1996, Hu et al. screened 38 patients with XLMTM for myotubularin 1 (MTM1) gene deletions located at Xq28. They found two unrelated boys with MTM1 deletions and unexpected abnormal genital development (Hu et al. 1996). This observation was explained by a contiguous gene syndrome which simultaneously affected the MTM1 gene and nearby genes involved in male sexual development. Several similar cases were subsequently reported who had ambiguous genitalia (e.g., bilateral cryptorchidism, penoscrotal hypospadias) (Laporte et al. 1997; Bartsch et al. 1999).