Diagnostic strategy for familial and sporadic cases of neuropathy associated with 17p11.2 deletion

• Published in: Muscle & nerve Vol. 24; no. 9; pp. 1149 - 1155
• Main Authors: Infante, Jon, García, Antonio, Combarros, Onofre, Mateo, José I., Berciano, José, Sedano, María J., Gutiérrez-Rivas, Eduardo J., Palau, Francesc
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.09.2001; Wiley
• Subjects: Adult; Aged; Biological and medical sciences; Charcot-Marie-Tooth Disease - diagnosis; Charcot-Marie-Tooth Disease - genetics; Child; chromosome 17p11.2 deletion; Chromosomes, Human, Pair 17; de novo mutation; electrodiagnosis; Electrodiagnosis. Electric activity recording; Family Health; Female; Gene Deletion; hereditary neuropathy with liability to pressure palsies; Humans; Investigative techniques, diagnostic techniques (general aspects); Male; Median Nerve - physiology; Medical sciences; Middle Aged; Nervous system; Neural Conduction; Paralysis - diagnosis; Paralysis - genetics; Pedigree; Peroneal Nerve - physiology; sporadic cases; Sural Nerve - physiology; Ulnar Nerve - physiology; Chromosomal aberration; Human; Nervous system diseases; Cubital nerve; Asymptomatic; Polyneuropathy; Genetic disease; Nerve conduction; Electrodiagnosis; Abnormal chromosome E17; Demyelination; Deletion; Abnormal chromosome; Genetics; Peripheral nerve disease; Paralysis; Tomaculous neuropathy; Sural nerve
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.1126

Clinical, electrophysiologic and molecular studies were performed on at‐risk members of 14 families with hereditary neuropathy with liability to pressure palsies (HNPP), in order to detect asymptomatic carriers of the 17p11.2 deletion. Sporadic cases due to de novo deletion accounted for 21% of the investigated HNPP families. Approximately one half of deletion carriers were asymptomatic and did not display significant signs on clinical examination. The electrophysiologic hallmark in both symptomatic and asymptomatic deletion carriers was the presence of a nonuniform sensorimotor demyelinating polyneuropathy with conduction abnormalities preferentially located at common entrapment sites and distal nerve segments. A perfect correlation was found between the molecular and electrophysiologic analyses. A reliable screening method to detect clinically unaffected carriers of the deletion in families with HNPP was the evaluation of motor conduction in at least two nerves across usual entrapment sites, especially the ulnar nerve at the elbow, and evaluation of sensory conduction in the sural nerve. In sporadic cases due to a de novo deletion, electrophysiologic studies were suggestive but not sufficient for the diagnosis, and molecular analysis represented the most sensitive diagnostic tool. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1149–1155, 2001