Prenatal ultrasound findings of holoprosencephaly spectrum: Unusual associations

Prenat Diagn. 2020 Apr;40(5):565-576. doi: 10.1002/pd.5649. Epub 2020 Feb 10.

Abstract

Objective: The objective of this study is to evaluate the prenatal diagnosis, postnatal characteristics, and the spectrum of associated findings in fetuses with holoprosencephaly (HPE).

Methods: Fetal neurosonograms, postnatal assessment, and chromosomal analysis were performed in a cohort of 25 fetuses with HPE.

Results: The prevalence of HPE in high-risk pregnancies was 4.4:10 000. The alobar subtype was the most frequently encountered, with 17 cases (68%). Interestingly, among them, four cases (16%) presented with the rare agnathia-otocephaly complex. Chromosomal abnormalities were detected in 11 cases (44%), the most frequent being trisomy 13 in seven cases (five alobar, one semilobar, and one lobar HPE), followed by trisomy 18 in two cases with semilobar HPE. One case of alobar HPE had 45, XX, t(18;22) (q10;q10), -18p karyotyping, and one case of semilobar HPE was associated with triploidy. Facial malformations in HPE spectrum ranged from cyclopia, proboscis, and arrhinia that were associated with the alobar subtype to hypotelorism and median cleft that were frequent among the semilobar and lobar subtypes. Associated neural tube defects were identified in 12% of cases.

Conclusion: Our study illustrates the clinical and genetic heterogeneity of HPE and describes different chromosomal abnormalities associated with HPE.

MeSH terms

  • Abortion, Induced
  • Adolescent
  • Adult
  • Chromosome Disorders / diagnostic imaging
  • Chromosome Disorders / epidemiology*
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 22
  • Consanguinity
  • Craniofacial Abnormalities / diagnostic imaging
  • Craniofacial Abnormalities / epidemiology*
  • Egypt / epidemiology
  • Encephalocele / diagnostic imaging
  • Encephalocele / epidemiology
  • Female
  • Fetal Death
  • Hernia, Umbilical / diagnostic imaging
  • Hernia, Umbilical / epidemiology*
  • Holoprosencephaly / diagnostic imaging
  • Holoprosencephaly / epidemiology*
  • Humans
  • Male
  • Neural Tube Defects / diagnostic imaging
  • Neural Tube Defects / epidemiology*
  • Pregnancy
  • Pregnancy in Diabetics / epidemiology
  • Prevalence
  • Translocation, Genetic
  • Triploidy
  • Trisomy 13 Syndrome / diagnosis
  • Trisomy 13 Syndrome / epidemiology
  • Trisomy 18 Syndrome / diagnosis
  • Trisomy 18 Syndrome / epidemiology
  • Ultrasonography, Prenatal
  • Young Adult

Supplementary concepts

  • Otocephaly
  • cyclopia sequence