Neurofibromatosis Type I

Inherited as an autosomal-dominant disorder with frequent new mutations (up to 50%), neurofibromatosis type I is caused by mutation in the neurofibromin gene located on chromosome 17q11.2. It is a relatively frequent disease with population estimates of 1 in 3400. A frequency of 1 in 390 has been found in young Israeli adults in a survey of military recruits (Table 22).

Table 21

Minor Diagnostic Criteria of Respiratory Chain Disorders Clinical

Symptoms compatible with a respiratory chain (RC) defect" Histology

1 to 2% Ragged red fibers if aged 30-50 years. Any ragged red fibers if younger than 30 years of age.

More than 2% subsarcolemmal mitochondrial accumulations in a patient younger than 16 years of age. Widespread electron microscopic abnormalities in any tissue. Enzymology

Antibody-based demonstration of a defect in RC complex expression. 20-30% Activity of any RC complex in a tissue. 30-40% Activity of any RC complex in a cell line. 30-40% Activity of the same RC complex activity in at least two tissues. Functional

Fibroblast adenosine triphosphate synthesis rates 2 to 3 standard deviations below mean. Fibroblasts unable to grow on media with glucose replaced by galactose. Molecular

Identification of a nuclear or mitochondrial DNA mutation of probable pathogenicity. Metabolic

One or more metabolic indicators of impaired RC function.

aIn addition to the symptoms listed elsewhere, we regarded pediatric features such as stillbirth associated with a paucity of intrauterine movement, neonatal death or collapse, movement disorder, severe failure to thrive, neonatal hypotonia, and neonatal hypertonia as minor clinical criteria. The adult criteria required muscle or neurologic involvement, but these do not have to be present in the modified general criteria.

Modifications to the original adult diagnostic criteria (Walker UA, Collins S, Byrne E. Respiratory chain encephalomy-opathies: a diagnostic classification. Eur Neurol 1996;36:260-267) that were developed in this study are shown in italics.

(Adapted with permission from Bernier FP, Boneh A, Dennett X, Chow CW, Cleary MA, Thorburn DR. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 2002;59:1406-1411.)

Table 22

Diagnostic Criteria for Neurofibromatosis Type 1

Two or more filled criteria are diagnostic.

1. Six or more café au lait spots, larger than 5 mm in diameter in prepubertal, and larger than 15 mm in diameter in postpubertal individuals.

2. Two or more neurofibromas of any type or one plexiform neurofibroma.

3. Axillary and/or inguinal freckling.

4. Optic nerve glioma.

5. Osseous lesions, such as dysplasia of the sphenoid wing, thinning of long bone cortex, with or without pseudoarthrosis.

6. First-degree relative (parent, sibling, or offspring) with neurofibromatosis type 1, according to above criteria.

Adapted from the National Institute of Neurological Disorders and Stroke. Available at

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