X-Linked Intellectual Disability-Hypotonic Face Syndrome

Mental retardation-hypotonic facies covers a group of X-linked syndromes characterized by severe intellectual deficit and facial dysmorphism, with variable other features.

Epidemiology

Prevalence is unknown but most of these syndromes have been reported in only a few families.

Clinical description

At present this group includes the Juberg-Marsidi, Carpenter-Waziri, Holmes-Gang, Renier-Gabreels-Jasper, Smith-Fineman-Myers and Chudley-Lowry syndromes (see these terms).

Etiology

These syndromes are caused by a mutation in the helicase 2 (XH2/ATRX; Xq13.3) gene.

Differential diagnosis

These syndromes show clinical similarity to alpha-thalassemia-X-linked mental retardation (ATR-X syndrome; see this term), which is also caused by a mutation in the ATRX gene, but all patients with a mental retardation-hypotonic facies syndrome display normal haematologic indices and do not appear to exhibit the haemoglobin H inclusions characteristic of ATR-X.

Genetic counseling

Transmission is X-linked recessive. A highly skewed X-inactivation pattern was identified in female carriers and some of the heterozygous mothers were reported to have manifestations such as subnormal intelligence and microcephaly.