The physical appearance of the patient can be very helpful in determining a diagnosis.

Dysmorphisms

A high forehead is suggestive of:

• a peroxisomal disorder (e.g., Zellweger syndrome or neonatal adrenoleukodystrophy)
• lissencephaly
• fragile X syndrome

Frontal bossing may suggest:

• Hurler’s syndrome
• GM1 gangliosidosis
• mucolipidosis II (I-cell disease)
• multiple sulfatase deficiency

Microcephaly is characteristic of:

• Angelman’s syndrome
• Cockayne’s syndrome
• Smith-Lemli-Opitz syndrome
• Rett syndrome

Other causes of cerebral and somatic dysmorphism associated with epilepsy include:

• glutaric aciduria type II
• hypomelanosis of Ito
• Lowe syndrome
• molybdenum cofactor deficiency
• pyruvate dehydrogenase deficiency
• tuberous sclerosis

Hair and skin defects

Defects in hair and skin are also important clues:

• Loss of hair: biotinidase deficiency and Cockayne’s syndrome
• Other anomalies of hair: mucopolysaccharidoses, Menkes’ syndrome, argininosuccinic aciduria
• Nodular lesions on the face, depigmented macules: tuberous sclerosis
• Café au lait spots and neurofibromas: neurofibromatosis
• Streaked, whirled, and mottled areas of hyperpigmentation: hypomelanosis of Ito
• Thin, atrophic skin: Cockayne’s syndrome

A Wood’s lamp examination of the skin for hypopigmentation should, therefore, be a routine part of the workup of a child who is experiencing seizures.

Growth failure

Growth failure is a common feature of many hereditary metabolic diseases. Short stature is found in patients with:

• mucopolysaccharidoses
• mucolipidoses
• mitochondrial encephalopathies
• Leigh disease
• MELAS
• myoclonic epilepsy with ragged red fibers (MERFF)

Enlarged liver

Hepatomegaly with liver dysfunction may be a sign of:

• Wilson’s disease
• Alpers-Huttenlocher syndrome
• Niemann-Pick disease type C

The liver is enlarged early in the course of Niemann-Pick disease types A and B, but liver failure occurs only as a late sequela. Liver failure is found also in certain mitochondrial disorders and in Zellweger syndrome.

Splenomegaly in an infant with seizures will suggest type 2 Gaucher’s disease. A later onset is typical of type 3 Gaucher’s disease.

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).
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.