Turner et al. (1994) reported a large 5-generation family in which several males had moderate to profound mental retardation consistent with X-linked inheritance. Several carrier females had mild mental retardation. Affected hemizygous males and heterozygous females had macrocephaly. ... Turner et al. (1994) reported a large 5-generation family in which several males had moderate to profound mental retardation consistent with X-linked inheritance. Several carrier females had mild mental retardation. Affected hemizygous males and heterozygous females had macrocephaly. Variable features included limited extension of the elbows and tapering fingers. There were 2 cases of holoprosencephaly in male infants. Froyen et al. (2008) reported 2 additional affected families. In 1 family, 3 males presented with moderate mental retardation. One was able to work in a sheltered environment and learned to read. As a child he had speech and language delay and clumsy motor skills. He was not dysmorphic, but had a long face and pointed chin. His affected male cousin had a similar phenotype. Neither had macrocephaly. An unrelated family demonstrated severe to profound mental retardation. Two brothers had no speech or language. One had flexion deformity of the knees, but was able to walk. An affected uncle lived in a residential home and had severe knee contractures. None had macrocephaly. Johnson et al. (1998) reported a large family in which 10 males spanning 2 generations had moderate mental retardation. Two females, who were sibs of affected males, were described as 'slow.' Four of 6 males studied had macroorchidism, and 5 had macrocephaly, but 1 affected male had normal testes. However, 2 unaffected males also had macroorchidism and macrocephaly, suggesting that these traits may have segregated independently in this family.
In affected individuals of the family reported by Turner et al. (1994), Froyen et al. (2008) identified a mutation in the HUWE1 gene (300697.0001). Affected individuals in 2 additional families were also found to have mutations in the ... In affected individuals of the family reported by Turner et al. (1994), Froyen et al. (2008) identified a mutation in the HUWE1 gene (300697.0001). Affected individuals in 2 additional families were also found to have mutations in the HUWE1 gene (300697.0002; 300697.0003).