title: GNAS-associated disorders of cutaneous ossification: two different clinical presentations.
abstract: Progressive osseous heteroplasia (POH) is a rare genetic disorder characterized by dermal ossification during infancy and progressive ossification into deep connective tissue during childhood. POH is at the severe end of a spectrum of GNAS-associated ossification disorders that include osteoma cutis and Albright Hereditary Osteodystrophy (AHO). Here we describe two girls who have different clinical presentations that reflect the variable expression of GNAS-associated disorders of cutaneous ossification. Each girl had a novel heterozygous inactivating mutation in the GNAS gene. One girl had POH limited to the left arm with severe contractures and growth retardation resulting from progressive heterotopic ossification in the deep connective tissues. The other girl had AHO with widespread, superficial heterotopic ossification but with little functional impairment. While there is presently no treatment or prevention for GNAS-associated ossification disorders, early diagnosis is important for genetic counselling and for prevention of iatrogenic harm.
authors.affiliation: Department of Paediatric Dermatology and Allergology, Wilhelmina's Children Hospital, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Schimmel
authors.forename: S G M A
authors.initials: SG
authors.lastname: Pasmans
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: S A E
authors.initials: SA
authors.lastname: Stadhouders-Keet
authors.forename: E M
authors.initials: EM
authors.lastname: Shore
authors.forename: F S
authors.initials: FS
authors.lastname: Kaplan
authors.forename: N M
authors.initials: NM
authors.lastname: Wulffraat
mesh_terms: D000293:Adolescent; D002648:Child; D002864:Chromogranins; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D009154:Mutation / Q000235:genetics; D009999:Ossification, Heterotopic / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D012867:Skin / Q000473:pathology
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs