Stiff skin syndrome is characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness (Loeys et al., 2010).
Patients with ... Stiff skin syndrome is characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness (Loeys et al., 2010). Patients with similar phenotypes involving stiff skin have been described; see, e.g., familial progressive scleroderma (181750), symmetric lipomatosis (151800), and congenital fascial dystrophy (228020).
Esterly and McKusick (1971) described a disorder characterized by thickened and indurated skin of the entire body and limitation of joint mobility with flexion contractures. One patient they reported was a sporadic case but the other had an ... Esterly and McKusick (1971) described a disorder characterized by thickened and indurated skin of the entire body and limitation of joint mobility with flexion contractures. One patient they reported was a sporadic case but the other had an affected sister and mother. Syndesmodysplasic dwarfism (272450) and the Parana hard-skin syndrome (260530) bear similarities to this syndrome but are apparently distinct recessive entities. Singer et al. (1977) reported a family with transmission through at least 4 generations and father-son involvement. Pichler (1968) described a father, daughter and son with flexion deformities of fingers and toes, limited motion of several other joints and the vertebral column, sclerodermatoid changes of the skin, and generalized increase in the consistence of otherwise slightly underdeveloped muscles. Suspected myosclerosis could not be confirmed by biopsy. The appearance of the affected son rather suggested that of pseudo-Hurler polydystrophy (252600) but no corneal changes were described and autosomal dominant inheritance seems likely. Stevenson et al. (1984) described a kindred in which many members had stiff skin beginning in adulthood. The presence of symmetrical lipomatosis suggested to the authors that this is the disorder described in entry 151800. Loeys et al. (2010) studied 4 families segregating autosomal dominant stiff skin syndrome with high penetrance, including a family with 10 affected individuals over 5 generations. All affected individuals displayed diffusely thick and hard skin from the time of birth and had developed joint contractures. Additional clinical features not previously described for stiff skin syndrome included cutaneous nodules that predominantly affected the distal interphalangeal joints, relative short stature, and diffuse entrapment neuropathy, with nerve injury and dysfunction due to local compression. None of the patients had skeletal, ocular, or cardiovascular findings of Marfan syndrome (MFS; 154700). However, Loeys et al. (2010) also examined a 14-year-old boy with a 'hybrid' phenotype, who had ocular lens dislocation, which is a cardinal manifestation of Marfan syndrome, glaucoma, retinal detachment, and tight skin with diffuse joint contracture. The boy, who was 1 of fraternal triplets, was considerably shorter than his unaffected brothers and displayed none of the skeletal or cardiovascular manifestations of MFS.
Loeys et al. (2010) sequenced the FBN1 gene (134797) in probands from 4 unrelated families with stiff skin syndrome and identified heterozygous missense mutations in each, all within exon 37 of the gene (see 134797.0050-134797.0053, respectively). Another patient ... Loeys et al. (2010) sequenced the FBN1 gene (134797) in probands from 4 unrelated families with stiff skin syndrome and identified heterozygous missense mutations in each, all within exon 37 of the gene (see 134797.0050-134797.0053, respectively). Another patient who had a 'hybrid' phenotype of stiff skin syndrome with ectopia lentis was found to be heterozygous for a missense mutation in exon 38 of FBN1 (134797.0054). None of the mutations were found in more than 400 ethnically matched controls.