Microcephaly, Autosomal Dominant

Description

Microcephaly strictly means abnormally small head size, but usually refers to an occipitofrontal head circumference below -2 SD from the mean for the infant's gestational age, sex, and ethnic origin. Microcephaly may appear as an isolated trait or in association with other malformations. It may also be sporadic or familial. Some familial cases are autosomal dominant, but most appear to be recessive (see 251200) (summary by Merlob et al., 1988).

Clinical Features

Rossi and Battilana (1982) reported microcephaly in 5 females in 3 generations. Intelligence was normal. Ramirez et al. (1983) described 13 cases of 'silent microcephaly' (microcephaly without neurologic or dysmorphic features and without mental retardation) in 3 unrelated families. Direct transmission with male-to-male inheritance was noted in each family. Rossi et al. (1987) described 6 Italian families with microcephaly without mental retardation and with an apparently autosomal dominant mode of inheritance. Merlob et al. (1988) found isolated microcephaly in 13 members of 3 generations of a large family. There were no other dysmorphic or neurologic abnormalities. There was 1 instance of male-to-male transmission and 1 instance of a nonmanifesting heterozygote resulting in a 'skipped generation.'

Clinical Variability

Haslam and Smith (1979) described 4 families in which microcephaly occurred in a pedigree pattern consistent with autosomal dominant inheritance. One instance of male-to-male transmission was observed. Receding or small forehead, upslanting palpebral fissures, and prominent ears were features. Intellectual impairment was less severe than in autosomal recessive microcephaly (251200).

Burton (1981) described microcephaly in at least 3 generations of a black family and commented on the association of short stature (adult height 142 cm in 1 male and 135 cm in 1 female) and simple, protruding ears. The proband at 15 months showed horizontal nystagmus and alternating esotropia. The affected mother also had esotropia. Hennekam et al. (1992) described the combination of microcephaly and short stature with normal intelligence in 6 members of 3 generations of a Dutch family. They concluded that the condition is the same as that described by Burton (1981).

Evans (1991) described 6 cases of microcephaly, hypotelorism, malar hypoplasia, and normal intelligence in 4 generations of a family; there was no instance of male-to-male transmission. Winter (1993) reported a mother and 2 sons with a syndrome of microcephaly, short stature, broad thumbs and great toes, mild developmental delay, and a face he considered distinctive. An impressive feature of the face in the mother and at least 1 boy was a fullness in the region of the philtrum associated with maxillary overbite. Winter (1993) pointed to similarities to the cases reported by Bawle and Horton (1989) and Evans (1991), and reviewed autosomal dominant microcephaly syndromes.

Melamed et al. (1994) reported a patient with microcephaly, short stature, and normal intelligence who also had oligodontia, i.e., complete absence of third molars and mandibular permanent second molars.

Also see 181180.

History

Hecht and Kelly (1979) quoted a statement that 'during the 19th century, head sizes were on the national census questionnaire.'