Macrocephaly is defined as an occipitofrontal circumference (OFC) greater than the 98th percentile for age. Macrocephaly may occur for many reasons, including megalencephaly, hydrocephalus, cerebral edema, neoplasia, and structural anomalies. Syndromic forms of macrocephaly are often due to megalencephaly, which is defined as a brain weight/volume ratio greater than the 98th percentile for age due to hyperplasia of the central nervous system parenchyma (Haskins Olney 2007). Individuals with these forms of syndromic macrocephaly may also exhibit somatic overgrowth. Other features commonly observed in individuals with syndromic macrocephaly include developmental delay, hypotonia, increased risk for neoplasia, dysmorphic features, and birth defects (Haskins Olney 2007; Neylon et al., 2012; Verge and Mowat 2010). In many cases, macrocephaly and/or overgrowth are identified in the neonatal period, although in other cases the onset may be postnatal and not noted until childhood. In some cases, growth parameters may normalize in adulthood (Verge and Mowat 2010).
The clinical features of the macrocephaly/overgrowth syndromes included on this panel are variable and may overlap significantly. Additionally, mutations in a single gene may be associated with a broad spectrum of clinical presentations (clinical heterogeneity). A complete list of the disorders included on the Syndromic Macrocephaly/Overgrowth Panel is available in the table on the last page of this information sheet.