The Genetics and Sub‐classification of Microcephaly*

A problem in diagnosis of primary versus secondary microcephaly

“…In spite of its rare occurrence, the importance of making a precise diagnosis of primary microcephaly for the sole purpose of genetic counseling cannot be overstated. A reliable objective criterion for achieving this aim, however, remains to be found (Cowie 1960). The present study investigated similarities and differences between primary microcephaly and secondary microcephaly on the basis of family and birth histories and clinical examinations.…”

“…Primary (genetic) microcephaly, however, is uncommon, with an estimated incidence of 1:25,000 to 1:50,000 (Book et al 1953, Komai et al 1955) and probably accounts for 0.5 to 1 percent of institutionalized mental defectives (Book et al 1953). Almost all instances of genetic microcephaly conform to an autosomal recessive mode of inheritance, and it is speculated that within this category more than one type may exist (Cowie 1960). Komai et al (1955) and Van den Bosch (1959) have drawn attention to the preponderance of males among primary microcephalics.…”

“…Thc problem of distinguishing between genetic microcephaly and its phenocopies has long presented a challenge. Although a number of clinical signs have been suggested as being characteristic of genetic microcephaly, there is n o agreement among authorities about application of these criteria for diagnosis (Cowie 1960). The suggestion (Penrose 1938) that eases of genetic microcephaly have low cephalic index (ratio of head width t o head length) was not confirmed by Brandon et al (1959), or by Qazi & Reed (1966).…”

Dominant inheritance of microcephaly with short stature

“…Congenital microcephaly is a relatively common malformation which may have either a genetic or an environmental etiology (Cowie 1960). Most cases of familial microcephaly appear to be inherited in an auto-soma1 recessive fashion (Koch 1959, Komai et al 1955, McKusick 1978.…”

Microcephaly: a review of genetic implications in its causation

“…Alongside evidence for clinical heterogeneity, there are strong indications that this group is genetically heterogeneous and that more than one gene is involved in recessive microcephaly (Brandon et al, 1959;Cowie, 1960). While some observers have found a sex ratio close to unity (Hanhart, 1958;Koch, 1959), others have found a preponderance of males.…”