title: Association of mutations in FLNA with craniosynostosis.
abstract: Mutations of FLNA, an X-linked gene that encodes the cytoskeletal protein filamin A, cause diverse and distinct phenotypes including periventricular nodular heterotopia and otopalatodigital spectrum disorders (OPDS). Craniofacial abnormalities associated with OPDS include supraorbital hyperostosis, down-slanting palpebral fissures and micrognathia; craniosynostosis was previously described in association with FLNA mutations in two individual case reports. Here we present four further OPDS subjects who have pathological FLNA variants and craniosynostosis, supporting a causal link. Together with the previously reported patients, frontometaphyseal dysplasia was the most common clinical diagnosis (four of six cases overall); five patients had multiple suture synostosis with the sagittal suture being the most frequently involved (also five patients). No genotype-phenotype correlation was evident in the distribution of FLNA mutations. This report highlights the need to consider a filaminopathy in the differential diagnosis of craniosynostosis, especially in the presence of atypical cranial or skeletal features.
authors: Craniofacial Unit, Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, UK.
authors: Nathalie
authors: N
authors: Fennell
authors: Wessex Clinical Genetics Services, UHS NHS Foundation Trust, Princess Anne Hospital, Southampton, UK.|Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
authors: Nicola
authors: N
authors: Foulds
authors: Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield, UK.
authors: Diana S
authors: DS
authors: Johnson
authors: Department of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors: Louise C
authors: LC
authors: Wilson
authors: Department of Paediatric Otolaryngology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors: Michelle
authors: M
authors: Wyatt
authors: Department of Women's and Children's Health, Dunedin School of Medicine, Dunedin, New Zealand.
authors: Stephen P
authors: SP
authors: Robertson
authors: Craniofacial Unit, Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, UK.
authors: David
authors: D
authors: Johnson
authors: Craniofacial Unit, Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, UK.
authors: Steven A
authors: SA
authors: Wall
authors: Craniofacial Unit, Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford, UK.|Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors: Andrew O M
authors: AO
authors: Wilkie
mesh_terms: D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D064448:Filamins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010641:Phenotype
chemical_list: C578663:FLNA protein, human; D064448:Filamins