Mental Retardation, X-Linked, Syndromic, Martin-Probst Type

Clinical Features

Martin et al. (2000) reported 3 related males with congenital sensorineural hearing loss, mental retardation, short stature, congenital umbilical hernia, facial dysmorphism, abnormal teeth, widely spaced nipples, and abnormal dermatoglyphics. The 2 older males developed progressive pancytopenia in adulthood. The mode of transmission was consistent with X-linked recessive inheritance, with maternally related affected males and clinically normal obligate carrier females. Variable renal and genitourinary abnormalities were found in this family (Martin et al., 2000; Probst et al., 2004). The youngest patient showed congenital bifid scrotum, small undescended testicles and phallus, chordee, and absence of the vas deferens and epididymis. Dysplasia of the left kidney was found by abdominal ultrasound at birth. Proteinuria was identified at the age of 11, and he was treated with angiotensin-converting enzyme inhibitors to prevent hyperfiltration through the right kidney. The oldest patient, 54 years of age at the time of the first report, had died from end-stage renal disease before the second report.

Inheritance

The transmission pattern in the family with X-linked mental retardation reported by Martin et al. (2000) was consistent with X-linked recessive inheritance.

Mapping

Martin et al. (2000) determined that the 3 males with the deafness-mental retardation syndrome described by them shared a haplotype between DXS1003 and DXS1220, a 68-Mb interval spanning Xq1-q21. In the carrier mothers of the 3 affected males reported by Martin et al. (2000), Probst et al. (2004) found skewed X inactivation.

Molecular Genetics

Associations Pending Confirmation

For discussion of a possible association between Martin-Probst X-linked mental retardation syndrome and variation in the RAB40AL gene, see 300405.0001.