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Restrictive dermopathy (RD) is a neonatal lethal genetic disease characterized by very tight and thin skin with erosions and scaling, associated to a typical facial dysmorphism, arthrogryposis multiplex, fetal akinesia or hypokinesia deformation sequence (FADS) (see these terms) and pulmonary hypoplasia without neurological abnormalities.
To date, approximately 80 children with RD have been described in the world literature.
RD is a congenital disorder and newborns are usually born prematurely (due to premature rupture of the membranes with subsequent delivery at about 30-32 weeks of gestation) with a very tight, thin, rigid and shiny skin with erosions and scaling, epidermal hyperkeratosis, prominent skin vessels, that results in limited joint movement and restricted growth of the underlying tissues, often rupturing and lacerating at flexure sites during delivery. Facial dysmorphism is also a characteristic feature of RD and includes telecanthus, short, down-slanting palpebral fissures, sparse/absent eyelashes and eyebrows, a small and pinched nose, posteriorly rotated low-set ears, micrognathia, and mouth fixed in the ''O'' position. Additional features include congenital anonychia (see this term), narrow chest, dysplastic clavicles, rocker-bottom feet and arthrogryposis multiplex. Intrauterine growth retardation (IUGR), polyhydramnios, decreased fetal movements, FADS, large placenta, neonatal teeth, choanal atresia, pterygium colli, patent arterial duct, interauricular communication (see these terms), dorsal kyphoscoliosis, camptodactyly, hypospadias, ureteral duplication, adrenal hypoplasia, have been occasionally reported. Pulmonary hypoplasia most often leads to respiratory insufficiency and death. Neither structural central nervous system nor visceral defects occur in RD.
RD can be caused by heterozygous, de novomutations of the LMNA (1q22) gene (primary laminopathy) or, much more frequently, by homozygous null mutations of the ZMPSTE24 (1p34) gene (secondary laminopathy). Defects in ZMPSTE24 impair the processing of prelamin A into mature lamin A, leading to the massive intranuclear accumulation of prelamin A isoforms which exert toxic effects and lead to the development of RD.
The rare mutations in the LMNA gene have a dominant effect (ZMPSTE24 mutations are inherited recessively, leading to the possibility of prenatal diagnosis for further pregnancies (25% risk of having another affected child for two mutation carriers), if the molecular bases of the disease are identified.