Frank-ter Haar syndrome associated with sagittal craniosynostosis and raised intracranial pressure
- Equal contributors
1 Oxford Craniofacial Unit, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK
2 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
3 Department of Clinical Genetics, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK
4 Cologne Center for Genomics, University of Cologne, Cologne, Germany
5 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
6 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
7 Current address: Department of Clinical Genetics, Great Ormond Street Hospital NHS Foundation Trust, WC1N 3BH, UK
BMC Medical Genetics 2012, 13:104 doi:10.1186/1471-2350-13-104Published: 9 November 2012
Frank-ter Haar syndrome is a rare disorder associated with skeletal, cardiac, ocular and craniofacial features including hypertelorism and brachycephaly. The most common underlying genetic defect in Frank-ter Haar syndrome appears to be a mutation in the SH3PXD2B gene on chromosome 5q35.1. Craniosynostosis, or premature fusion of the calvarial sutures, has not previously been described in Frank-ter Haar syndrome.
We present a family of three affected siblings born to consanguineous parents with clinical features in keeping with a diagnosis of Frank-ter Haar syndrome. All three siblings have a novel mutation caused by the deletion of exon 13 of the SH3PXD2B gene. Two of the three siblings also have non-scaphocephalic sagittal synostosis associated with raised intracranial pressure.
The clinical features of craniosynostosis and raised intracranial pressure in this family with a confirmed diagnosis of Frank-ter Haar syndrome expand the clinical spectrum of the disease. The abnormal cranial proportions in a mouse model of the disease suggests that the association is not coincidental. The possibility of craniosynostosis should be considered in individuals with a suspected diagnosis of Frank-ter Haar syndrome.