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Hereditary motor and sensory neuropathy (HMSN) IA, developmental delay and autism related disorder in a boy with

U Moog1, J J Engelen, B W Weber

  • 1Department of Clinical Genetics, Research Institute Growth & Development (GROW), Maastricht University, Maastricht, The Netherlands. ute.moog@gen.unimaas.nl

Genetic Counseling (Geneva, Switzerland)
|April 16, 2004
PubMed

Insights

A de novo duplication on chromosome 17p11.2-p12 in a boy led to developmental delay, autism, and Charcot-Marie-Tooth type 1A (CMT1A) neuropathy. This duplication also caused distinctive facial features, confirming a known genetic syndrome.

Area of Science:

  • Genetics
  • Neurology
  • Developmental Pediatrics

Background:

  • Genetic duplications on chromosome 17p are associated with various neurodevelopmental disorders.
  • Charcot-Marie-Tooth type 1A (CMT1A) is a peripheral neuropathy often linked to duplications involving the PMP22 gene.
  • Smith-Magenis syndrome is a complex genetic disorder characterized by developmental delay and distinctive facial features.

Observation:

  • A 6-year-old boy presented with moderate developmental delay, gait disturbance, autism, and mild dysmorphic features.
  • Initial cytogenetic analysis revealed a normal karyotype, but further investigation identified a de novo duplication on 17p11.2-p12.
  • Neurological examination showed a motor and sensory polyneuropathy, diagnosed as hereditary motor and sensory neuropathy type Ia (HMSN Ia), a form of CMT1A.

Findings:

  • Quantitative Southern blot and FISH analysis confirmed a duplication encompassing the PMP22 locus, consistent with HMSN Ia.
  • Retrospective GTG banding re-evaluation and FISH analysis specifically for the Smith-Magenis region (17p11.2) revealed the 17p duplication.
  • The patient exhibited a recognizable facial phenotype including a broad forehead, hypertelorism, downslanting palpebral fissures, smooth philtrum, thin upper lip, and ear anomalies.

Implications:

  • This case reinforces the phenotypic spectrum of 17p11.2-p12 duplications, including psychomotor delay, neurobehavioral issues, and craniofacial anomalies.
  • The findings highlight the association between PMP22 locus duplications and HMSN Ia, underscoring the genetic basis of CMT1A.
  • The study contributes to understanding the genotype-phenotype correlation in dup(17)(p11.2) and dup(17)(p11.2p12) syndromes, aiding in diagnosis and genetic counseling.

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