A number sign (#) is used with this entry because of evidence that restrictive dermopathy-2 (RSDM2) is caused by heterozygous mutation in the LMNA gene (150330) on chromosome 1q22.

Restrictive dermopathy is a rare genodermatosis characterized mainly by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial dysmorphism (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures, and an early neonatal lethal course. Liveborn children usually die within the first week of life (summary by Navarro et al., 2004).

For a discussion of genetic heterogeneity of restrictive dermopathy, see RSDM1 (275210).

Navarro et al. (2004) reported 2 patients with restrictive dermopathy and mutation in the LMNA gene. Patient 1 (P1) was a female born to parents originating from Corsica (France) after 5 cycles of in vitro fertilization. Delivery occurred at 29 weeks' gestation by cesarean section for fetal distress and intrauterine growth retardation. Feeding difficulties, dysmorphism, and abnormal skin were present at birth. The skin was tight and sclerotic. There was joint retraction of the knees, hips, elbows, and digits, microretrognathism, and a beaked nose with proptosis. X-rays showed shortened hypoplastic clavicles, acroosteolysis of terminal phalanges, kyphosis of the spine, small facial bones, and overtubulated long bones and ribs. At age 4 months, rectal prolapse and bilateral hernia occurred. The patient died at 6 months due to respiratory distress. Skin biopsy showed a thickened skin with a flat dermis depleted of elastic fibers, hypertrophic endoplasmic reticulum in keratinocytes, and numerous collagen fibers at the dermoepidermal junction. Patient 2 (P2) was a female born to healthy unrelated parents of Moroccan and Algerian origin. Pregnancy was uneventful, with the exception of reduced fetal movements, and delivery was at term. At birth, the child's skin was edematous with rapidly developing erosions and scleroderma-like lesions. Blood vessels were apparent under the skin of the tibias; on the trunk, skin was taut, thick and slightly desquamating, whereas the venous bed was not prominent in this area. Microretrognathism with exophthalmia was present. Mouth movements were not limited; weeping caused gastroesophageal reflux and cyanosis, secondary to thoracic and abdominal restriction. Clavicular hypoplasia was observed at X-ray. The patient was alive at age 5 months but her clinical condition was poor.

The inheritance of restrictive dermatitis-2 in 2 patients reported by Navarro et al. (2004) was autosomal dominant. In patient 2, the heterozygous mutation was confirmed to have occurred de novo.

In 2 of 9 patients (P1 and P2) with restrictive dermopathy, Navarro et al. (2004) identified heterozygous splicing mutations in the LMNA gene, resulting in the complete or partial loss of exon 11 (150330.0036 and 150330.0022, respectively). In the other 7 patients, they identified a heterozygous 1-bp duplication resulting in a premature stop codon in the zinc metalloproteinase STE24 gene (ZMPSTE24; 606480.0001); see RSDM1 (275210). The ZMPSTE24 gene encodes a metalloproteinase specifically involved in the posttranslational processing of lamin A precursor. In all patients carrying a ZMPSTE24 mutation, loss of expression of lamin A as well as abnormal patterns of nuclear sizes and shapes and mislocalization of lamin-associated proteins was seen. Navarro et al. (2004) concluded that a common pathogenetic pathway, involving defects of the nuclear lamina and matrix, is involved in restrictive dermopathy.