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Phenotypic spectrum of NDE1 ‐related disorders: from microlissencephaly to microhydranencephaly
Author(s) -
AbdelHamid Mohamed S.,
ElDessouky Sara H.,
Ateya Mohamed I.,
Gaafar Hassan M.,
AbdelSalam Ghada M.H.
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61035
Subject(s) - phenotype , spectrum (functional analysis) , genetics , biology , physics , quantum mechanics , gene
Biallelic variants in the NDE1 gene have been shown to occur in extreme microcephaly. Most of the patients displayed microlissencephaly but one with microhydranencephaly. We report on three sibs in which the brain MRI and CT scans demonstrated variable degree of reduced volume of cerebral hemispheres and ventriculomegaly. Further, they had agenesis of corpus callosum, cerebellar, and brainstem hypoplasia. Fetal ultrasound at 32 weeks' gestation of the third sib revealed severe micrencephaly with extensive hydranencephaly and an anomaly consistent with non cleaved (fused) thalami. Because of the fused thalami, the STIL gene was targeted initially but showed negative results. His postnatal MRI showed that the cerebral hemispheres are markedly reduced in size (with no definite frontal, parietal, or occipital lobes) and replaced by a large sac filled with CSF. An intact falx cerebri was identified. This extensive hydarencephaly led us to consider the NDE1 and to identify a novel homozygous nonsense variant (c.54G>A, p.W18*). The variability of the degree of brain malformations and the apparent fusion of the thalami were illusive and delayed the recognition of the genetic etiology. Our results provide the first antenatal description of this rare syndrome. Further, we expand the genetic architecture and the neuroradiologic phenotype of NDE1 ‐related disorders.