Hedgehog acyl-transferase-related multiple congenital anomalies: Report of an additional family and delineation of the syndrome

Am J Med Genet A. 2021 Sep;185(9):2756-2765. doi: 10.1002/ajmg.a.62186. Epub 2021 Mar 22.


This study includes previous reports of four affected individuals from two unrelated families with hedgehog acyl-transferase (HHAT)-related multiple congenital anomaly syndrome. Microcephaly, small cerebellar vermis, holoprosencephaly, agenesis of corpus callosum, intellectual disability, short stature, skeletal dysplasia, microphthalmia-anophthalmia, and sex reversal constitute the phenotypic spectrum of this condition with variable expression. We report an additional family with three affected conceptuses: two abortuses and one living proband. We did proband-parents trio exome sequencing and identified a biallelic in-frame deletion c.365_367del; (p.Thr122del) in exon 5 of HHAT. With this report, we delineate the phenotype and allelic heterogeneity of the HHAT-related multiple congenital anomaly syndrome.

Keywords: HHAT; Nivelon-Nivelon-Mabille syndrome (NNMS); holoprosencephaly; microphthalmia; sex reversal; skeletal dysplasia.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology*
  • Acyltransferases / genetics*
  • Adult
  • Child
  • Child, Preschool
  • Congenital Abnormalities / genetics
  • Congenital Abnormalities / pathology*
  • Female
  • Fetal Diseases / genetics
  • Fetal Diseases / pathology*
  • Fetus / pathology*
  • Gene Deletion*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Pedigree
  • Young Adult


  • Acyltransferases
  • HHAT protein, human