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.
This is a preview of subscription content, log in via an institution to check access.
References
Antoine T (1929) Ein Fall von allgemeiner, angeborener Hautatrophie. Monatschr Geburtsh Gynakol 81:276–283
Armbrust S, Hoffmann R, Jochum F, Neumann LM, Fusch C (2005) Restrictive dermopathy associated with transposition of the great arteries and microcolon. Arch Dermatol 141:611–613 doi:10.1001/archderm.141.5.611
Bergo MO, Gavino B, Ross J et al (2002) Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc Natl Acad Sci U S A 99:13049–13054 doi:10.1073/pnas.192460799
Carmi R, Sofer S, Karplus M et al (1982) Aplasia cutis congenita in two sibs discordant for pyloric atresia. Am J Med Genet 11:319–328 doi:10.1002/ajmg.1320110308
Fong LG, Ng JK, Lammerding J et al (2006) Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest 116(3):743–752 doi:10.1172/JCI27125
Fong LG, Ng JK, Meta M et al (2004) Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc Natl Acad Sci U S A 101(52):18111–18116 doi:10.1073/pnas.0408558102
Hammond E, Donnenfeld AE (1995) Fetal akinesia. Obstet Gynecol Surv 50:240–249 doi:10.1097/00006254-199503000-00028
Kulkarni ML, Shetty KS, Chandrasekar VK, Preethi MK (2006) Restrictive dermatopathy: a lethal congenital dermatosis and review of literature. Am J Med Genet A 140(3):294–297 doi:10.1002/ajmg.a.20264
Leschot NJ, Treffers PE, Becker-Bloemkolk MJ, van Zanten S, de Groot WP, Verjaal M (1980) Severe congenital skin defects in a newborn. Case report and relevance of several obstetrical parameters. Eur J Obstet Gynecol Reprod Biol 10(6):381–388 doi:10.1016/0028-2243(80)90023-4
Mahadevan B, Karthikeyan K, Vishnu Bhat B, Thappa DM (2002) Restrictive dermopathy—a case report. Indian Pediatr 39:1149–1152
Mau U, Kendziorra H, Kaiser P, Enders H (1997) Restrictive dermopathy: report and review. Am J Med Genet 71:179–185 doi:10.1002/(SICI)1096-8628(19970808)71:2<179::AID-AJMG11>3.0.CO;2-B
Moessinger AC (1983) Fetal akinesia deformation sequence: an animal model. Pediatrics 72:857–863
Moulson CL, Gloriosa G, van der Wal AC, Sillevis Smitt JH, van Hagen JM, Miner JH (2005) Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy. J Invest Dermatol 125(5):913–919 doi:10.1111/j.0022-202X.2005.23846.x
Mulder EJH, Beemer FA, Stoutenbeek P (2001) Restrictive dermopathy and fetal behavior. Prenat Diagn 21:581–585 doi:10.1002/pd.89
Navarro CL, Cadiñanos J, De Sandre-Giovannoli A et al (2005) Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of lamin A precursors. Hum Mol Genet 14:1503–1513 doi:10.1093/hmg/ddi159
Navarro CL, De Sandre-Giovannoli A, Bernard R et al (2004) Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 13:2493–2503 doi:10.1093/hmg/ddh265
Nijsten TEC, De Moor A, Colpaert CG, Robert K, Mathieu LM, Lambert J (2002) Restrictive Dermopathy: a case report and a critical review of all hypotheses of its origin. Pediatr Dermatol 19(1):67–72 doi:10.1046/j.1525-1470.2002.00029.x
Pendas AM, Zhou Z, Cadiñanos J et al (2002) Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nat Genet 31:94–99
Smitt JH, van Asperen CJ, Niessen CM et al (1998) Restrictive dermopathy. Report of 12 cases. Arch Dermatol 134:577–579 doi:10.1001/archderm.134.5.577
Toriello HV (1986) Restrictive dermopathy and report of another case. Am J Med Genet 24:625–629 doi:10.1002/ajmg.1320240407
Toriello HV, Higgins JV, Waterman DF (1983) Autosomal recessive aplasia cutis congenita: a report of two affected sibs. Am J Med Genet 15:153–156 doi:10.1002/ajmg.1320150122
Van der Stege JG, van Straaten HLM, van der Wal AC, van Eyck J (1997) Restrictive dermopathy and associated prenatal ultrasound findings: case report. Ultrasound Obstet Gynecol 10:140–141 doi:10.1046/j.1469-0705.1997.10020140.x
Van Hoestenberghe M, Legius E, Vandevoorde W et al (1990) Restrictive dermopathy with distinct morphological abnormalities. Am J Med Genet 36:297–300 doi:10.1002/ajmg.1320360310
Verloes A, Mulliez N, Gonzales M et al (1992) Restrictive dermopathy, a letal form of arthogryposis multiplex with skin and bone dysplasias: three new cases and review of literature. Am J Med Genet 43:539–547 doi:10.1002/ajmg.1320430308
Wehnert M, Nguyen TD, Bethmann C, Hausser I, Albrecht B (2006) Mutational analysis of LMNA and ZMPSTE24 in restrictive laminopathy. Eur J Hum Genet 14(Suppl. 1):232
Welsh KM, Smoller BR, Kolbrook KA, Johnston K (1992) Restrictive dermopathy: report of two affected siblings and a review of literature. Arch Dermatol 128:228–231 doi:10.1001/archderm.128.2.228
Wepler W (1938) Zur Frage allgemeiner Hypoplasie der Haut. Beitr Pathol Anat 101:457–469
Witt DR, Hayden M, Holbrook KA, Dale BA, Baldwin VJ, Taylor GP (1986) Restrictive dermopathy: a newly recognized autosomal recessive skin dysplasia. Am J Med Genet 24:631–648 doi:10.1002/ajmg.1320240408
Young SG, Meta M, Yang SH, Fong LG (2006) Prelamin A farnesylation and progeroid syndromes. J Biol Chem 281(52):39741–39745 doi:10.1074/jbc.R600033200
Acknowledgments
The authors are grateful to Prof. F. Carvalho, Department of Genetics, Faculty of Medicine, University of Porto (Porto, Portugal) for assistance with the DNA extraction and to proband’s family for their interest and support in the investigations. The support of Huong Le Thi Thanh by the Joint Graduate Education Program of Deutscher Akademischer Austauschdienst (DAAD, VNM 04/A17) is acknowledged as well as the support of Manfred Wehnert by a grant of the German Ministry of Education and Research BMBF (01GM0302).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Morais, P., Magina, S., Ribeiro, M.d.C. et al. Restrictive dermopathy—a lethal congenital laminopathy. Case report and review of the literature. Eur J Pediatr 168, 1007–1012 (2009). https://doi.org/10.1007/s00431-008-0868-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-008-0868-x