Abstract
We evaluated a family with three siblings, two of whom ages 2 years and 19 months, had long segment colonic agangliosis and anisocoria. The mother also had anisocoria. All three affected family members were mildly dysmorphic with a flat facial profile, square appearance to the face, depressed nasal bridge, and anteverted nares. Genetic testing identified a novel heterozygous mutation, c.234C>G, resulting in a premature stop codon in exon 1 of the PHOX2B gene. Screening for neural crest tumors was performed in the siblings and to date has been negative. This family supports a strong association between non polyalanine tract mutations, autonomic dysfunction, and Hirschsprung disease, but suggests mutation outside of the polyalanine tract may not dictate severe phenotype with significant respiratory compromise. A unique finding in this family is the association of congenital heart disease in two of the affected patients. These malformations may be a sporadic isolated finding or the result of environmental factors or a modifying allele. Given the association between congenital heart disease and aberrant neural crest cell development, however, findings are suggestive that congenital heart disease may be a rare feature of PHOX2B mutation which has not been previously reported.
Original language | English (US) |
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Pages (from-to) | 1705-1709 |
Number of pages | 5 |
Journal | American Journal of Medical Genetics, Part A |
Volume | 173 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2017 |
Externally published | Yes |
Keywords
- congenital central hypoventilation syndrome
- congenital heart disease
- Hirschsprung
- neuroblastoma
- PHOX2B
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)