Thinking of VACTERL-H? Rule out Fanconi Anemia according to PHENOS

Am J Med Genet A. 2016 Jun;170(6):1520-4. doi: 10.1002/ajmg.a.37637. Epub 2016 Mar 30.

Abstract

VACTERL-H association includes three of eight features: vertebral anomalies, anal atresia, congenital heart disease, tracheo-esophageal fistula, esophageal atresia, renal, limb anomalies, and hydrocephalus. The VACTERL-H phenotype among cases with FA is considered to be about 5%; the frequency of FA among patients with VACTERL-H is unknown. We examined 54 patients with FA in the National Cancer Institute Inherited Bone Marrow Failure Syndrome Cohort for features of VACTERL-H, including imaging studies (radiology and ultrasound). Eighteen of the fifty-four patients had three or more VACTERL-H features. The presence of VACTERL-H association in 33% of those with FA is much higher than the previous estimate of 5% (P < 0.0001). We created the acronym PHENOS (Pigmentation, small Head, small Eyes, central Nervous system (not hydrocephalus), Otology, and Short stature) which includes all major phenotypic features of FA that are not in VACTERL-H; these findings were more frequent in the patients with FA who had VACTERL-H. Identification of any components of the VACTERL-H association should lead to imaging studies, and to consideration of the diagnosis of FA, particularly if the patient has radial ray and renal anomalies, as well as many features of PHENOS. There was no association of the presence or absence of VACTERL-H with development of cancer, stem cell transplant, or survival. Early diagnosis will lead to genetic counseling and early surveillance and management of complications of FA. © 2016 Wiley Periodicals, Inc.

Keywords: VACTERL-H; VATER; fanconi anemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Cardiovascular Abnormalities / diagnosis*
  • Cardiovascular Abnormalities / genetics*
  • Cardiovascular Abnormalities / mortality
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diagnosis, Differential
  • Digestive System Abnormalities / diagnosis*
  • Digestive System Abnormalities / genetics*
  • Digestive System Abnormalities / mortality
  • Fanconi Anemia / diagnosis*
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / mortality
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Female
  • Genetic Association Studies*
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / mortality
  • Genotype
  • Humans
  • Hydrocephalus / diagnosis*
  • Hydrocephalus / genetics*
  • Hydrocephalus / mortality
  • Male
  • Middle Aged
  • Musculoskeletal Abnormalities / diagnosis*
  • Musculoskeletal Abnormalities / genetics*
  • Musculoskeletal Abnormalities / mortality
  • Mutation
  • Phenotype*
  • Syndrome
  • Young Adult

Substances

  • Fanconi Anemia Complementation Group Proteins

Supplementary concepts

  • VACTERL Association With Hydrocephalus