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Elsahy–Waters syndrome is caused by biallelic mutations in CDH11
Author(s) -
Harms Frederike L.,
Nampoothiri Sheela,
Anazi Shams,
Yesodharan Dhanya,
Alawi Malik,
Kutsche Kerstin,
Alkuraya Fowzan S.
Publication year - 2018
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.38568
Subject(s) - craniofacial , phenotype , hypertelorism , genetics , medicine , biology , pathology , bioinformatics , gene
Elsahy–Waters syndrome (EWS), also known as branchial–skeletal–genital syndrome, is a distinct dysmorphology syndrome characterized by facial asymmetry, broad forehead, marked hypertelorism with proptosis, short and broad nose, midface hypoplasia, intellectual disability, and hypospadias. We have recently published a homozygous potential loss of function variant in CDH11 in a boy with a striking resemblance to EWS. More recently, another homozygous truncating variant in CDH11 was reported in two siblings with suspected EWS. Here, we describe in detail the clinical phenotype of the original CDH11 ‐related patient with EWS as well as a previously unreported EWS‐affected girl who was also found to have a novel homozygous truncating variant in CDH11 , which confirms that EWS is caused by biallelic CDH11 loss of function mutations. Clinical features in the four CDH11 mutation‐positive individuals confirm the established core phenotype of EWS. Additionally, we identify upper eyelid coloboma as a new, though infrequent clinical feature. The pathomechanism underlying EWS remains unclear, although the limited phenotypic data on the Cdh11 −/− mouse suggest that this is a potentially helpful model to explore the craniofacial and brain development in EWS‐affected individuals.