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).