Reynolds Syndrome

A number sign (#) is used with this entry because of evidence that Reynolds syndrome is caused by heterozygous mutation in the LBR gene (600024) on chromosome 1q42. One such patient has been reported.

Clinical Features

Reynolds et al. (1971) reported 6 unrelated women, ranging in age from 38 to 51 years, with a constellation of clinical features, including liver disease, telangiectasia, Raynaud phenomenon, and variable features of scleroderma (181750). The liver disease was characterized by pruritus, jaundice, hepatomegaly, increased serum alkaline phosphatase, and positive serum mitochondrial autoantibodies, all consistent with primary biliary cirrhosis (PBC; 109720). Liver biopsies showed variable subtle features of PBC, including absence of cholangioles and inflammatory cells, in most patients. Telangiectases were present on the fingerpads of all patients, on the lips in 5, and in the gastrointestinal tract in at least 2. Most patients described pain and blanching of the hands upon cold exposure, and all except 1 patient had sclerodactyly of the hands and forearms. Two had decreased esophageal motility, and 3 had areas of calcinosis cutis. These findings were reminiscent of CREST syndrome (see 181750). Three patients had upper gastrointestinal bleeding, which was related to telangiectasia or esophageal varices. Nonspecific symptoms included fatigue and generalized increase in skin pigmentation. None had a family history of the disorder. The association of PBC with a form of scleroderma suggested to Reynolds et al. (1971) an immunologic etiology for the liver disease.

Murray-Lyon et al. (1970) reported 2 unrelated women in their sixties with scleroderma affecting the hands and esophagus associated with PBC, telangiectasia, and Raynaud disease. One also had areas of calcinosis of the skin. Both had mitochondrial autoantibodies.

Gaudy-Marqueste et al. (2010) reported a 76-year-old Caucasian woman with Reynolds syndrome. She had a long history of Raynaud phenomenon, telangiectasia, and mild cholestasis. Laboratory studies showed autoimmune markers, such as increased erythrocyte sedimentation rate, antimitochondrial autoantibodies, and antinuclear antibodies. She had limited cutaneous scleroderma, and was diagnosed with PBC.

Molecular Genetics

In a 76-year-old Caucasian woman with Reynolds syndrome, Gaudy-Marqueste et al. (2010) identified a heterozygous mutation in the LBR gene (R372C; 600024.0007). Studies of patient lymphoblastoid cells did not show abnormalities, but patient fibroblasts showed decreased LBR and decreased levels of lamin proteins, as well as dysmorphic nuclei with mottled chromatin. These findings suggested that the R372C mutation exerted a dominant-negative effect on LBR-interacting proteins, perhaps resulting from decreased stabilization of the mutant protein and increased proteasome-mediated degradation.