Megalencephaly, Autosomal Dominant
Description
Primary megalencephaly is defined as a head circumference about the 98th percentile that most likely is due to brain enlargement and is not secondary to disease (review by Petersson et al., 1999).
Clinical FeaturesDeMyer (1972) reported instances of apparently autosomal dominant megalencephaly, with male-to-male transmission in some cases. In a family with megalencephaly in 3 generations, the proband also had mediastinal ganglioneuroblastoma. Macrocephaly predominated in males.
Schreier et al. (1974) found 10 persons in 3 generations of a family with presumed megalencephaly. An additional 2 members were considered to have true hydrocephalus.
Among 557 children who presented a diagnostic problem of a large head, Lorber and Priestley (1981) found 109 with megalencephaly as the primary diagnosis. At least half the cases had a familial incidence of large head. Males predominated 4 to 1. Only 7 of the 109 were mentally retarded and these showed also a variety of neurologic and other somatic abnormalities; some had superior intelligence.
InheritanceAutosomal dominant inheritance was suggested by DeMyer (1972) and Schreier et al. (1974).
Fryns et al. (1988) reported the cases of 3 sisters with mental retardation, macrocephaly, and coarse facies. Since the mother and maternal grandfather had similar macrocephaly, Fryns et al. (1988) suggested autosomal dominant inheritance.