title: Variable expression of campomelic dysplasia in a father and his 46, XY daughter.
abstract: Campomelic dysplasia (CD, MIM 114290) is characterised by widespread osseous abnormalities including bowing of the long bones, dysplasia of the cartilage of the tracheobronchial tree, and neurological abnormalities leading to high perinatal lethality. A majority of karyotypic males present as phenotypic females. The disorder has only recently been categorised as a dominantly transmitted entity after demonstration of heterozygous mutations in the SOX9 gene on chromosome 17q24.3 or translocations associated with breakpoints upstream of this gene. Despite this mode of transmission, only two well-documented instances of parent-child transmission of the disorder have been described. We report a man of normal intelligence with mild phenotypic and radiological appearances of CD. His first-born child, a phenotypic female with a 46,XY karyotype, presented with significantly more severe skeletal and neurological involvement. Parents of individuals with CD should be examined for minimal manifestations of the disorder, which may represent phenotypic variability in the syndrome or somatic mosaicism.
authors.affiliation: Victorian Clinical Genetics Services, Royal Children's Hospital and University of Melbourne, Parkville, Victoria 3052, Australia. savarirr@cryptic.rch.unimelb.edu.au
authors.forename: Ravi
authors.initials: R
authors.lastname: Savarirayan
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.forename: Agnes
authors.initials: A
authors.lastname: Bankier
authors.forename: John G
authors.initials: JG
authors.lastname: Rogers
mesh_terms: D002675:Child, Preschool; D012734:Disorders of Sex Development; D005220:Fathers; D005260:Female; D006609:High Mobility Group Proteins; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009030:Mosaicism / Q000235:genetics; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging* / Q000235:genetics*; D011859:Radiography; D055758:SOX9 Transcription Factor; D014157:Transcription Factors
chemical_list: D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors