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Failure of ossification of the occipital bone in mandibuloacral dysplasia type B
Author(s) -
Haye Damien,
Dridi Hend,
Levy Jonathan,
Lambert Véronique,
Lambert Maurice,
Agha Mohamed,
Adjimi Frédéric,
Kohlhase Jürgen,
Lipsker Dan,
Verloes Alain
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37825
Subject(s) - lipodystrophy , ossification , medicine , dysplasia , short stature , heterotopic ossification , polydactyly , anatomy , pathology , endocrinology , family medicine , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy
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.