PAK3 related mental disabillity:: Further characterization of the phenotype

We report clinical, neuropsycological and molecular findings in affected males and carrier females in the fourth reported family with mental retardation caused by mutation in the PAK3 gene reported family with mental retardation caused by mutation in the PAK3 gene (Xq22.3-q23), W446s in the PAK3 gene (Xq22.3-cl23), W446S. in contrast to previous reports, carrier females manifested learning problems and mild mental disability. Skewed X-inactivation was observed here for the first time in carriers of PAK 3 mutation. Neuropsychologic,. tests in affected males and carrier females suggested a common neuropsycological profile of impaired spatial females suggested a common neuropsychological profile of impaired spatial cognitive abilities and defects in attentional and execcutive functions. The five affected males examined herein had a proportional, small head size or microcephaly , large cars oral motor hypotonia with drooling and inarticulate speech and short attention span, anxiety, restlesness, and aggression Brain imaging showed signs of chronic non-progressive hydrocephalus in one patient who manifested psychosis and fluctant gait cleterioration, while two other patients showed no abnormalities. EEG recordings were available from four affected males and one carrier fertile, and all showed similar posterior slow -wave activity without epileptic discharges. Only one affected male in the family suffered front epilepsy. When comparing the affected males in this Family and the three previously reported families with mental retardation due to I PAK3 imitation, similarities in their characteristics were small head size or microcephaly, large ears, speech defects,behavioral abnormalities,and psychiatric disease. (C) 2007 Wiley-Liss, Inc.