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Caput membranaceum: A novel clinical presentation of ZIC1 related skull malformation and craniosynostosis
Author(s) -
Sasaki Erina,
Byrne Angela T.,
Murray Dylan J.,
Reardon William
Publication year - 2020
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.61882
Subject(s) - craniosynostosis , microcephaly , skull , medicine , anterior fontanelle , hypophosphatasia , craniosynostoses , zinc finger , anatomy , biology , gene , genetics , pediatrics , transcription factor , biochemistry , alkaline phosphatase , enzyme
We report clinical and radiological features of a patient born with an isolated skull malformation of caput membranaceum and partial bicoronal craniosynostosis with a novel, de novo heterozygous missense variant in ZIC1 [NM_003412.3:c.1183C>G, p.(Pro395Ala)]. Caput membranaceum, or boneless skull, is a rare manifestation of skull ossification defect. It can result from an isolated, enlarged parietal foramina or it can present as part of skeletal dysplasia syndromes associated with poor mineralization such as hypophosphatasia, osteogenesis imperfecta type II, and Saethre‐Chotzen syndrome. Their causative genes are well described. ZIC1 , Zinc Finger protein of the cerebellum 1 (OMIM #600470) belongs to ZIC family genes, each encoding a Cys2 His2‐type zinc finger domain‐containing transcription factors. Recent studies have shown that pathogenic variants in ZIC1 have deleterious effect in developing human central nerves system and skull bone. ZIC1 related clinical conditions are reported and include cerebellum malformation, Dandy‐Walker malformation, spinal dysraphism, microcephaly, and craniosynostosis with associated intellectual disability. To‐date, there is no report of pathogenic variant in ZIC1 causing isolated caput membranaceum. Our observation adds to the clinical spectrum of ZIC1 related skull malformation.