title: Frontometaphyseal dysplasia and keloid formation without FLNA mutations.
abstract: Frontometaphyseal dysplasia (FMD) is a distinctive sclerosing skeletal dysplasia associated with a number of non-skeletal manifestations including hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. Some, but not all, patients have mutations in FLNA causing the condition. Consonant with the X chromosomal location of FLNA males are generally more severely affected than females. FLNA mutations can be detected in 82% of affected males. We describe seven patients (one male, six females) all of whom have the major clinical and radiological features of FMD, but without detectable mutations in FLNA. The females in our cohort are affected to a similar degree as is usually found in males. In addition, all patients have marked keloid formation at various body sites, including the eye, from an early age. Other features that may indicate a different etiology in these patients are the increased frequency of cleft palate, Robin sequence, tracheal stenosis, and mild intellectual disability, which all occur in three of more patients in the present group. All patients are isolated. We hypothesize that the presently reported patients represent further evidence that phenotypes strongly resembling FMD exist that are not accounted for by mutations in FLNA. Since the frequency of several of the manifestations, their sporadic presentations, and the presence of keloid formation differ from the X-linked form of this condition we propose de novo autosomal dominant acting mutations in a gene functionally related to FLNA, underpin this disorder.
authors.affiliation: Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Plastic and Reconstructive Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Basart
authors.affiliation: Department of Plastic and Reconstructive Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annekatrien
authors.initials: A
authors.lastname: van de Kar
authors.affiliation: Discipline of Pediatrics and Child Health, Department of Clinical Genetics, University of Sydney, The Children's Hospital, Westmead, Sydney, Australia.
authors.forename: Lesley
authors.initials: L
authors.lastname: Adès
authors.affiliation: Division of Pediatric Orthopedics, Seoul National University Children's Hospital, Seoul, Republic of Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.affiliation: Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias, Hospital for Special Surgery, New York, New York.
authors.forename: Erin
authors.initials: E
authors.lastname: Carter
authors.affiliation: Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saskia M
authors.initials: SM
authors.lastname: Maas
authors.affiliation: Clinical Genetics Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Wilson
authors.affiliation: Department of Plastic and Reconstructive Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Chantal M A M
authors.initials: CM
authors.lastname: van der Horst
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Wade
authors.affiliation: Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.affiliation: Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Hennekam
mesh_terms: D000293:Adolescent; D002648:Child; D058674:Chromosome Duplication; D002892:Chromosomes, Human, Pair 22; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D005260:Female; D064448:Filamins / Q000235:genetics; D005546:Forehead / Q000002:abnormalities* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D007627:Keloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010855:Pierre Robin Syndrome / Q000235:genetics* / Q000473:pathology; D012737:Sex Factors; D014135:Tracheal Stenosis / Q000235:genetics* / Q000473:pathology
chemical_list: C578663:FLNA protein, human; D064448:Filamins
keywords: Robin sequence; cleft palate; filamin A; frontometaphyseal dysplasia; hypertrophic scar; intellectual disability; keloid; otopalatodigital spectrum disorder