title: Restrictive dermopathy--a lethal congenital laminopathy. Case report and review of the literature.
abstract: Restrictive dermopathy (RD) is a rare, fatal, and genetically heterogeneous laminopathy with a predominant autosomal recessive heredity pattern. The phenotype can be caused by mutations in either LMNA (primary laminopathy) or ZMPSTE24 (secondary laminopathy) genes but mostly by homozygous or compound heterozygous ZMPSTE24 mutations. Clinicopathologic findings are unique, allowing a specific diagnosis in most cases. We describe a premature newborn girl of non-consanguineous parents who presented a rigid, translucent and tightly adherent skin, dysmorphic facies, multiple joint contractures and radiological abnormalities. The overall clinical, radiological, histological, and ultrastructural features were typical of restrictive dermopathy. Molecular genetic analysis revealed a homozygous ZMPSTE24 mutation (c.1085_1086insT). Parents and sister were heterozygous asymptomatic carriers. We conclude that RD is a relatively easy and consistent clinical and pathological diagnosis. Despite recent advances in our understanding of RD, the pathogenetic mechanisms of the disease are not entirely clarified. Recognition of RD and molecular genetic diagnosis are important to define the prognosis of an affected child and for recommending genetic counseling to affected families. However, the outcome for a live born patient in the neonatal period is always fatal.
authors.affiliation: Department of Dermatology and Venereology, Hospital S João, Alameda Professor Hernâni Monteiro, Porto, Portugal. paulomoraiscardoso@gmail.com
authors.forename: Paulo
authors.initials: P
authors.lastname: Morais
authors.forename: Sofia
authors.initials: S
authors.lastname: Magina
authors.forename: Maria do Céu
authors.initials: Mdo C
authors.lastname: Ribeiro
authors.forename: Manuela
authors.initials: M
authors.lastname: Rodrigues
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.forename: Huong Le Thi
authors.initials: Hle T
authors.lastname: Thanh
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehnert
authors.forename: Hercília
authors.initials: H
authors.lastname: Guimarães
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D004547:Elastic Tissue / Q000002:abnormalities* / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D034904:Lamin Type A / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics*; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000473:pathology
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D008565:Membrane Proteins; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human