A new X-linked mental retardation (XLMR) syndrome with late-onset primary testicular failure, short stature and microcephaly maps to Xq25–q26

X-linked mental retardation (XLMR) is a heterogeneous disorder with both syndromic and non-syndromic forms. Here we describe the clinical and molecular characterisation of a family with a syndromic form of XLMR with hypogonadism and short stature. We investigated a family in which four male members in two generations presented with hypergonadotrophic hypogonadism associated with development of small and abnormal testes. In two of the males, late-onset testicular ascent was noted. In addition, all affected males had short stature (<0.4th centile) and mild learning difficulties and three out of the four had microcephaly. Karyotypes were normal and endocrine investigations confirmed primary testicular failure.The phenotype segregated as an X-linked trait. Haplotype and genetic two-point linkage analysis with 22 microsatellites excluded the whole X chromosome except for a region on Xq25–Xq27 encompassing 13.7 Mb with a maximum LOD score of 1.1 for marker DXS8038 at θ = 0.05.One family previously described as having XLMR with hypogonadism and short stature maps to the same X chromosome region implicated in our family. However, the more severe mental retardation, muscle wasting and tremor described in this other family would suggest that our family is affected by a novel XLMR syndrome.