Syndromic Alobar Holoprosencephaly Associated with a de novo 2p21p16.2 Contiguous Gene Deletion: A Neonatal Case
Ramazan Keçeci1, Hayriye Nermin Keçeci2, Melek Büyükeren1
1Division of Neonatology, Department of Pediatrics, Konya City Hospital, University of Health Science, Konya, Turkey.
Background:
Chromosome 2p21 harbors SIX3, a major driver gene for holoprosencephaly (HPE). Large copy number variants (CNVs) overlapping 2p21p16.2 are rare and may present with pleiotropic congenital anomalies.
Case Presentation:
A female neonate born at 27 weeks (1,000 g) after placental abruption was diagnosed with distinguishable craniofacial features, alobar HPE, agenesis of the corpus collosum (ACC), and a 6-mm atrial septal defect. Chromosomal microarray analysis revealed a heterozygous 11.3 Mb interstitial deletion at arr[GRCh38] 2p21p16.2(43075433_54379379)x1, containing entire SIX3, EPCAM, and a cluster of mismatch repair (MMR) genes such as MSH2 and MSH6. The parents do not have dysmorphic features, their karyotype analysis was normal, and based on the available data, the CNV was considered de novo.
Conclusion:
The patient's phenotype is consistent with SIX3 haploinsufficiency leading to severe forebrain division insufficiency; the adjacent MMR deletion defines the Lynch susceptibility locus. We emphasize the need to consider the risk of cancer in later life, in addition to the currently available findings.
Related Concept Videos
01:43Sex-linked Disorders
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:33Pleiotropy
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:43Sex Linked Disorders