MACROCEPHALY, EPILEPSY, AUTISM, DYSMORPHIC FEATURES, AND MENTAL-RETARDATION IN 2 SISTERS - A NEW AUTOSOMAL RECESSIVE SYNDROME

We report two sisters with macrocephaly, epilepsy, and severe mental r etardation. The first child was a 14 year aid girl born at term after a normal pregnancy, with birth weight 3600 g and occipitofrontal circu mference (OFC) 36 cm (75th centile). Her head size increased markedly during the first six months of life, and was later stable at 2-3 cm ab ove the 97.5th centile. Her development was characterised by psychomot or delay, epilepsy, and autistic features. Her face appeared mildly dy smorphic with a large forehead, short philtrum, and bushy eyebrows. He r younger sister was also born at term with birth weight 2600 g and OF C 34 cm (25th centile). She also developed postnatal macrocephaly with OFC 1 cm above the 97.5th centile and the same mild dysmorphic facial features au her sister. Her development was also characterised by psy chomotor delay, autistic features, and epilepsy. In addition, she suff ered from coeliac disease. She died unexpectedly at the age of 5 years ,:probably from an epileptic attack. Necropsy confirmed megalencephaly but no other pathological changes were found. The clinical features i n these two sisters do not fit with any known syndrome and may represe nt a previously unrecognised autosomal recessive disorder.