title: Muenke syndrome: An international multicenter natural history study.
abstract: Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal, and calcaneal fusions, and behavioral differences. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings. Muenke syndrome constitutes the most common syndromic form of craniosynostosis, with an incidence of 1 in 30,000 births and is defined by the presence of the p.Pro250Arg mutation in FGFR3. Participants were recruited from international craniofacial surgery and genetic clinics. Affected individuals, parents, and their siblings, if available, were enrolled in the study if they had a p.Pro250Arg mutation in FGFR3. One hundred and six patients from 71 families participated in this study. In 51 informative probands, 33 cases (64.7%) were inherited. Eighty-five percent of the participants had craniosynostosis (16 of 103 did not have craniosynostosis), with 47.5% having bilateral and 28.2% with unilateral synostosis. Females and males were similarly affected with bicoronal craniosynostosis, 50% versus 44.4% (P = 0.84), respectively. Clefting was rare (1.1%). Hearing loss was identified in 70.8%, developmental delay in 66.3%, intellectual disability in 35.6%, attention deficit/hyperactivity disorder in 23.7%, and seizures in 20.2%. In patients with complete skeletal surveys (upper and lower extremity x-rays), 75% of individuals were found to have at least a single abnormal radiographical finding in addition to skull findings. This is the largest study of the natural history of Muenke syndrome, adding valuable clinical information to the care of these individuals including behavioral and cognitive impairment data, vision changes, and hearing loss.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
authors.forename: Paul
authors.initials: P
authors.lastname: Kruszka
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
authors.forename: Yonit A
authors.initials: YA
authors.lastname: Addissie
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
authors.forename: Colin M P
authors.initials: CM
authors.lastname: Yarnell
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Hadley
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Guillen Sacoto
authors.affiliation: Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Platte
authors.affiliation: Department of Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Paelecke
authors.affiliation: Section of Pediatric Neurosurgery, Department of Neurosurgery, University of Würzburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Collmann
authors.affiliation: Sydney Children's Hospital, University of New South Wales, Sydney, Australia.|Kinghorn Centre for Clinical Genomics, The Garvan Institute, Darlinghurst, Sydney, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Snow
authors.affiliation: Section of Pediatric Neurosurgery, Department of Neurosurgery, University of Würzburg, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Schweitzer
authors.affiliation: Department of Pediatrics, Section of Genetics, University of California Davis, Sacramento, California.
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
authors.affiliation: Department of Clinical Genetics, Akademiska University Hospital, Uppsala, Sweden.
authors.forename: Christos
authors.initials: C
authors.lastname: Aravidis
authors.affiliation: Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Hall
authors.affiliation: Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.affiliation: Section of Pediatric Neurosurgery, Department of Neurosurgery, University of Würzburg, Germany.|Sydney Children's Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Roscioli
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, The National Institutes of Health, Bethesda, Maryland.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D056973:Four-Dimensional Computed Tomography; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D055815:Young Adult
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: FGFR3-related craniosynostosis; Muenke syndrome; craniosynostosis