title: Cerebro-costo-mandibular syndrome: Clinical, radiological, and genetic findings.
abstract: Cerebro-Costo-Mandibular syndrome (CCMS) is a rare autosomal dominant condition comprising branchial arch-derivative malformations with striking rib-gaps. Affected patients often have respiratory difficulties, associated with upper airway obstruction, reduced thoracic capacity, and scoliosis. We describe a series of 12 sporadic and 4 familial patients including 13 infants/children and 3 adults. Severe micrognathia and reduced numbers of ribs with gaps are consistent findings. Cleft palate, feeding difficulties, respiratory distress, tracheostomy requirement, and scoliosis are common. Additional malformations such as horseshoe kidney, hypospadias, and septal heart defect may occur. Microcephaly and significant developmental delay are present in a small minority of patients. Key radiological findings are of a narrow thorax, multiple posterior rib gaps and abnormal costo-transverse articulation. A novel finding in 2 patients is bilateral accessory ossicles arising from the hyoid bone. Recently, specific mutations in SNRPB, which encodes components of the major spliceosome, have been found to cause CCMS. These mutations cluster in an alternatively spliced regulatory exon and result in altered SNRPB expression. DNA was available from 14 patients and SNRPB mutations were identified in 12 (4 previously reported). Eleven had recurrent mutations previously described in patients with CCMS and one had a novel mutation in the alternative exon. These results confirm the specificity of SNRPB mutations in CCMS and provide further evidence for the role of spliceosomal proteins in craniofacial and thoracic development.
authors.affiliation: Department of Clinical Genetics, St. Michael's Hospital, Bristol, United Kingdom.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Tooley
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Lynch
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Bernier
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Canada.
authors.forename: Jillian
authors.initials: J
authors.lastname: Parboosingh
authors.affiliation: Department of Clinical Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bhoj
authors.affiliation: Department of Clinical Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.affiliation: Department of Radiology, Great Ormond Street Children's Hospital, London, United Kingdom.
authors.forename: Alistair
authors.initials: A
authors.lastname: Calder
authors.affiliation: Centre for Comparative and Clinical Anatomy, University of Bristol, Bristol, United Kingdom.
authors.forename: Nobue
authors.initials: N
authors.lastname: Itasaki
authors.affiliation: North West Thames Regional Genetic Service, North West London Hospitals NHS Trust, London, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Wakeling
authors.affiliation: Department of Clinical Genetics, Great Ormond Street Children's Hospital, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Scott
authors.affiliation: Department of Clinical Genetics, Great Ormond Street Children's Hospital, London, United Kingdom.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lees
authors.affiliation: Department of Clinical Genetics, St. Mary's Hospital, Manchester, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.affiliation: Department of Clinical Genetics, Chapel Allerton Hospital, Leeds, United Kingdom.
authors.forename: Moira
authors.initials: M
authors.lastname: Blyth
authors.affiliation: Department of Clinical Genetics, Birmingham Women's Hospital, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Morton
authors.affiliation: Department of Clinical Genetics, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Debbie
authors.initials: D
authors.lastname: Shears
authors.affiliation: Department of Clinical Genetics, Churchill Hospital, Oxford, United Kingdom.
authors.forename: Usha
authors.initials: U
authors.lastname: Kini
authors.affiliation: Department of Clinical Genetics, St. George's Hospital, London, United Kingdom.
authors.forename: Tessa
authors.initials: T
authors.lastname: Homfray
authors.affiliation: Department of Clinical Genetics, University Hospital Wales, Cardiff, United Kingdom.
authors.forename: Angus
authors.initials: A
authors.lastname: Clarke
authors.affiliation: Department of Clinical Genetics, Great Ormond Street Children's Hospital, London, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Barnicoat
authors.affiliation: Department of Paediatric Respiratory Medicine, Great Ormond Street Children's Hospital, London, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Wallis
authors.affiliation: Department of Paediatric Respiratory Medicine, Great Ormond Street Children's Hospital, London, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hewitson
authors.affiliation: Academic Unit of Child Health, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
authors.forename: Amaka
authors.initials: A
authors.lastname: Offiah
authors.affiliation: Department of Otolaryngology, St. Michael's Hospital, Bristol, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Saunders
authors.affiliation: Department of Paediatric Respiratory Medicine, Bristol Royal Hospital for Children, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Langton-Hewer
authors.affiliation: Department of Paediatric Respiratory Medicine, Bristol Royal Hospital for Children, London, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Hilliard
authors.affiliation: Department of Paediatric Intensive Care, Bristol Royal Hospital for Children, Bristol, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Davis
authors.affiliation: Department of Clinical Genetics, St. Michael's Hospital, Bristol, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Smithson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002972:Cleft Palate / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008844:Micrognathism / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D012272:Ribs / Q000002:abnormalities* / Q000254:growth & development / Q000503:physiopathology; D012600:Scoliosis / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D017381:Spliceosomes / Q000235:genetics; D055517:snRNP Core Proteins / Q000235:genetics*
chemical_list: C526407:SNRPB protein, human; D055517:snRNP Core Proteins
keywords: CCM syndrome; Cerebro-costo-mandibular syndrome; Pierre Robin syndrome; micrognathia; rib gaps