Restrictive Dermopathy, Lethal

Alternative Names

  • Tight Skin Contracture Syndrome, Lethal
  • Hyperkeratosis-Contracture Syndrome
  • Fetal Hypokinesia Sequence due to Restrictive Dermopathy
Back to search Result
WHO-ICD-10 version:2010

Diseases of the skin and subcutaneous tissue

Other disorders of the skin and subcutaneous tissue

OMIM Number

275210

Mode of Inheritance

Autosomal recessive

Gene Map Locus

1p34.2; 1q22

Description

Restrictive Dermopathy is a lethal autosomal recessive genodermatosis, in which extremely taut skin leads to in utero growth retardation and reduced fetal movements. Affected fetuses and patients have a tightly adherent skin, which is thin and translucent. They also show a typical facies, generalized joint contractures, enlarged fontanelles, clavicular dysplasia, respiratory insufficiency, and an enlarged placenta with a short umbilical cord. The skin abnormalities lead to fetal akinesia or hypokinesia deformation sequence, resulting in premature delivery at around 31 weeks gestational age. Histologic abnormalities include abnormal maturation of the epidermis, dermis, hypodermis, and cutaneous appendages. The dermis is thin with compactly arranged collagen bundles and scant elastic fibers. There is paucity and hypoplasia of the appendages. The epidermal rete ridges are flattened and the dermal-hypodermal border is remarkably straight.

The cutaneous abnormalities do not appear until 22-24 weeks' gestational age. Therefore, prenatal diagnosis is not very easy. Differential diagnoses for restrictive dermopathy include other disorders of fetal akinesia, including Pena-Shokeir syndrome, COFS syndrome, Parana Hard-Skin syndrome, and Hutchinson-Gilfor Progeria syndrome. Affected patients are either still-born or survive only a few weeks after birth. The ultimate cause of death is usually respiratory insufficiency.

Molecular Genetics

Restrictive Dermopathy is an autosomal recessive condition. Two related, but different genes have been implicated in the pathogenesis of this disorder. These are the LMNA (Lamin A) and ZMPSTE24 (Zinc Metalloproteinase STE24) genes. The LMNA gene codes for the Lamin A protein, which is a major structural component of the inner nuclear membrane scaffolding, and plays a role in chromatin organization, transcription, and mitosis. The ZMPSTE24 protein plays a major role in the post-translational processing of mature Lamin A proteins. The precise molecular pathway through which mutations in these two genes result in the phenotypic abnormalities seen in restrictive dermopathy is not clear. It has been suggested that defects in the function of Lamin A protein could result in changes in gene expression patterns consequent to chromatin re-organization. This could result in the pathology associated with this disease.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
275210.1.1United Arab EmiratesMaleYesYes Death in infancy; Wide anterior fontane... NM_005857.5:c.627+1G>CHomozygousAutosomal, RecessiveSander et al. 2008
275210.1.2United Arab EmiratesMaleYesYes Death in infancy; Wide anterior fontan... NM_005857.5:c.627+1G>CHomozygousAutosomal, RecessiveSander et al. 2008 Fourth cousin of 275...

Other Reports

Algeria

Verloes et al. (1992) described three unrelated affected stillborn infants, each with consanguineous parents. Two of them were of Algerian ancestry and one Turkish. Clinical findings included a tight, thin, translucent skin which tore spontaneously in flexion creases, arthrogryposis multiplex congenita (which included the temporomandibular joint), enlarged fontanels, typical face, and dysplasia of clavicles and long bones. Histologic abnormalities included hyperplastic, abnormally keratinized epidermis, reduced tonofilaments, thin, compact dermis with hypoplasia of the elastic fibers, and abnormal subcutaneous fat.

United Arab Emirates

Sander et al. (2008) reported two Emirati patients diagnosed with restrictive dermopathy. Both patients were born to consanguineous parents, belonged to the same tribe, and were related by way of their grandparents being second-cousins. The patients were born at 31 and 33 weeks gestational age. They were noted to have large anterior fontanelles, micrognathia, thin fragile and shiny skin with prominent veins, and marked joint contractures. Despite ventilation, both patients died in the second month of their lives. Skin biopsy of patient 1 revealed a flat epidermis with lack of rete edges and an orthokeratotic stratum corneum. Dermis appeared thin and dense due to abnormally compact collagen bundles and scant elastic fibers. There were few rudimentary hair follicles. Both patients were found to carry homozygous mutations in the ZMPSTE24 gene.

© CAGS 2021. All rights reserved.