title: Failure of ossification of the occipital bone in mandibuloacral dysplasia type B.
abstract: Mandibuloacral dysplasia with type B lipodystrophy is a rare autosomal recessive disease characterized by atrophic skin, lipodystrophy, and skeletal features. It is caused by mutations in ZMPSTE24, a gene encoding a zinc metalloproteinase involved in the post-translational modification of lamin. Nine distinct pathogenic variants have been identified in 11 patients from nine unrelated families with this disorder. We report a 12-year-old boy with mandibuloacral dysplasia with type B lipodystrophy and a novel homozygous c.1196A>G; p.(Tyr399Cys) mutation in ZMPSTE24. The patient had typical dermatological and skeletal features of mandibuloacral dysplasia with type B lipodystrophy, sparse hair, short stature, mild microcephaly, facial dysmorphism, and a striking failure of ossification of the interparietal region of the occipital bone, up to the position where transverse occipital suture can be observed. Newly recognized signs for mandibuloacral dysplasia with type B lipodystrophy were gaze palsy and ptosis. Delayed closure of cranial sutures and Wormian bones have been described in three patients, but an ossification failure strictly limited to the occipital bone, as seen in the present patient, appears to be unique for mandibuloacral dysplasia with type B lipodystrophy. This observation illustrates that ZMPSTE24 could play a specific role in membranous ossification in the interparietal part of the squama (Inca bone) but not in the intracartilaginous ossification of the supraoccipital. This failure of ossification in the squama appears to be a useful feature for the radiological diagnosis of mandibuloacral dysplasia with type B lipodystrophy. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital and Paris VII-Denis Diderot Medical School Paris, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Haye
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital and Paris VII-Denis Diderot Medical School Paris, Paris, France.
authors.forename: Hend
authors.initials: H
authors.lastname: Dridi
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital and Paris VII-Denis Diderot Medical School Paris, Paris, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levy
authors.affiliation: Regional Hospital, Saint Laurent du Maroni, French Guiana, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lambert
authors.affiliation: Medical Doctor, Saint Laurent du Maroni, French Guiana, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Lambert
authors.affiliation: Medical Doctor, Mana, French Guiana, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Agha
authors.affiliation: Regional Hospital, Saint Laurent du Maroni, French Guiana, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Adjimi
authors.affiliation: Center for Human Genetics Freiburg, Freiburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
authors.affiliation: Department of Dermatology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Lipsker
authors.affiliation: Department of Genetics, APHP-Robert Debré University Hospital and Paris VII-Denis Diderot Medical School Paris, Paris, France. alain.verloes@aphp.fr.|Sorbonne-Paris Cité University, Denis Diderot Medical School and INSERM UMR 1141 PROTECT, Paris, France. alain.verloes@aphp.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D001706:Biopsy; D001842:Bone and Bones / Q000473:pathology; D002648:Child; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008060:Lipodystrophy / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D009154:Mutation; D009777:Occipital Bone / Q000473:pathology*; D010012:Osteogenesis / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D012867:Skin / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D008565:Membrane Proteins; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human
keywords: ZMPSTE24; mandibuloacral dysplasia; wormian bones