Restrictive dermopathy

Restrictive dermopathy (also known as lethal tight skin contracture syndrome or lethal restrictive dermopathy) is an extremely rare and almost invariably fatal congenital disorder primarily affecting the skin and multiple organ systems. It is caused by mutations in the ZMPSTE24 gene (which encodes a metalloproteinase involved in lamin A processing) or, less commonly, by mutations in the LMNA gene. The disease belongs to the group of laminopathies — disorders related to defects in nuclear lamin proteins. The hallmark feature is taut, rigid, translucent skin that severely restricts fetal movement in utero, leading to fetal akinesia or hypokinesia deformation sequence. Affected neonates present with characteristic tightly adherent, thin, and erosion-prone skin, a fixed facial expression, small pinched nose, micrognathia (small jaw), and a small mouth. Joint contractures (arthrogryposis) are prominent, and the lungs are typically hypoplastic due to restricted thoracic movement during fetal development. Additional features include intrauterine growth restriction, sparse or absent eyelashes and eyebrows, mineralization defects of the skull (wide fontanelles and sutures), and prominent superficial blood vessels visible through the translucent skin. Clavicular dysplasia may also be observed. The prognosis for restrictive dermopathy is extremely poor. Most affected infants are stillborn or die within the first few days to weeks of life, primarily due to respiratory insufficiency caused by pulmonary hypoplasia and the inability to expand the chest wall. There is currently no curative treatment, and management is limited to supportive and palliative care. Genetic counseling is essential for affected families, and prenatal diagnosis is possible through molecular testing when the familial mutation is known.

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