Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency

Clin Genet. 2000 May;57(5):388-93. doi: 10.1034/j.1399-0004.2000.570510.x.

Abstract

We report an infant with holoprosencephaly (HPE), sacral anomalies, and situs ambiguus with a 46,XY,der(7)t(2;7)(p23.2;q36.1) karyotype as a result of an adjacent-1 segregation of a t(2;7)pat. The chromosomal abnormality was diagnosed prenatally after sonographic detection of HPE in the fetus. The baby was born at 37 weeks gestation, and died in the newborn period; he had dysmorphic features consistent with HPE sequence. Postmortem internal evaluation showed semilobar HPE, abdominal situs ambiguus, multiple segments of bowel atresia, dilatation of the ureters, and bony sacral anomalies. Molecular analysis confirmed hemizygosity for the SHH and HLXB9 genes, which are likely to be responsible for the HPE and sacral phenotypes, respectively. Immunohistochemical studies showed intact dopaminergic pathways in the mesencephalon, suggesting that midbrain dopamine neuron induction appears to require only one functioning SHH allele.

Publication types

  • Case Reports

MeSH terms

  • Abdomen / abnormalities*
  • Abdomen / pathology
  • Abnormalities, Multiple / genetics
  • Chromosomes, Human, Pair 2*
  • Chromosomes, Human, Pair 7*
  • Genes, Homeobox / genetics*
  • Hedgehog Proteins
  • Holoprosencephaly / diagnostic imaging
  • Holoprosencephaly / genetics*
  • Holoprosencephaly / pathology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Male
  • Monosomy / genetics*
  • Proteins / genetics*
  • Radiography, Abdominal
  • Sacrococcygeal Region / abnormalities*
  • Sacrococcygeal Region / diagnostic imaging
  • Sacrococcygeal Region / pathology
  • Trans-Activators*
  • Trisomy / genetics*

Substances

  • Hedgehog Proteins
  • Proteins
  • SHH protein, human
  • Trans-Activators