Primary Delayed Onset Craniosynostosis in a Child With ERF-Related Craniosynostosis Syndrome and Familial Cerebral Cavernous Malformation Syndrome

Abstract

Primary delayed onset craniosynostosis is defined as premature suture fusion that developed despite clear radiographic evidence of normal postnatal calvarial configuration and patent sutures earlier in life. It is rare in the literature and typically presents as secondary synostosis. In this brief clinical study, primary delayed onset craniosynostosis is described in its unique presentation at 4 years of age with a complex genetic history including ERF-related craniosynostosis syndrome and familial cerebral cavernous malformation syndrome. Although the delayed onset clinical course of ERF-related craniosynostosis syndrome has not been well described in the literature, our review suggests that it is distinctive to ERF-related craniosynostosis and should be considered when cases present without a history of trauma, when there is a positive family history, and particularly when cases present late onset; after 1 year of age.

An Ultra-Rare Mixed Phenotype with Combined AP-4 and ERF Mutations: The First Report in a Pediatric Patient and a Literature Review

“…To date, several types of mutations have been identified in the AP4B1 gene among individuals with AP-4 deficiency syndrome. Most of these mutations predictably result in a loss of AP-4 function, impairing the transport of proteins and lipids within cells [5]. Some of the variants identified in the AP4B1 gene are missense mutations, altering a single amino acid in the AP4B1 protein [15], while others are nonsense mutations or frameshift mutations disrupting normal protein production [4].…”

“…The ERF gene, also recognized as the ETS2 repressor factor gene, is responsible for encoding a transcriptional repressor crucial in the development and differentiation of various tissues, including bone and cartilage. Pathogenic alterations within the ERF gene have been linked to an infrequent autosomal dominant disorder identified as ERF-related craniosynostosis [5][6][7].…”