A family history is a useful place to start. Parental consanguinity can raise the presumption of an autosomal recessive disease. More than one affected sibling or close relative in a family also is suggestive of a familial disorder. Availability of a family pedigree provides an opportunity to counsel unaffected family members concerning their own risk for having the disease or for carrying the abnormal gene.

A maternal inheritance pattern may be a clue to an X-linked disorder, such as Menkes’ syndrome, or to the transmission of a defect in mitochondrial DNA, as in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

Phenotypic heterogeneity can occur even within the same family, so that differences in symptomatology and time course of the illness can be found among siblings receiving the same diagnosis, as in adrenoleukodystrophy and globoid cell leukodystrophy.

Adapted from: Kolodny, EH. Metabolic and genetic disorders. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;17–22.
With permission from Elsevier (www.elsevier.com).