Rienhoff (pronounced REENhoff) syndrome is a congenital syndrome characterized by abnormal development of several mesenchymal-derived tissues, including muscle and craniopalatofacial structures, accompanied by low muscle mass, growth retardation, distal arthrogryposis, and other secondary changes. The syndrome shares some ... Rienhoff (pronounced REENhoff) syndrome is a congenital syndrome characterized by abnormal development of several mesenchymal-derived tissues, including muscle and craniopalatofacial structures, accompanied by low muscle mass, growth retardation, distal arthrogryposis, and other secondary changes. The syndrome shares some clinical features with known syndromes that enhance TGF-beta signaling, such as the Marfan (see 154700) and Loeys-Dietz (see 609192) syndromes, including arachnodactyly, pectus excavatum, pes planus, and hyperextensible large joints, as well as hypertelorism and bifid uvula; however, there is no evidence of vascular disease (summary by Rienhoff et al., 2013).
Rienhoff et al. (2013) described a 9-year-old European American girl, born to nonconsanguineous parents, whose birthweight was in the 5th centile with length and head circumference in the 50th centiles; in addition, she was noted to have contractures ... Rienhoff et al. (2013) described a 9-year-old European American girl, born to nonconsanguineous parents, whose birthweight was in the 5th centile with length and head circumference in the 50th centiles; in addition, she was noted to have contractures of the hands and feet, most severe in the third and fourth fingers of the right hand, and mild hypotonia. At 17 months of age, her weight was below the 1st centile with height in the 5th centile, and she could not crawl or roll, but could stand with support. She had bilateral pes planus, mild pectus excavatum, hyperextensibility of the large joints, and mild retrognathia. There was a small metopic ridge, and her eyes were prominent, with blue sclerae and hypertelorism, and she had a tubular nose. Her skin was of normal texture, tension, and wound healing. She had a bifid uvula with intact hard palate, normal arch, and normal voice quality. There were marked contractures of the proximal phalangeal joints of the right second and third digits and toes bilaterally, more severe on the right. Motor examination revealed decreased bulk in all appendicular and axial muscles, decreased strength, low tone, and diminished reflexes throughout; in addition, there was markedly reduced subcutaneous fat. A 3-year trial of losartan produced no change in muscle strength or mass. At 7 years of age, her weight was still below the 1st centile and height in the 5th centile, and the physical examination was unchanged. Muscle biopsy showed a normal checkerboard pattern with type 1 fiber predominance, but there was mild focal type 1 fiber disproportion consistent with disuse or decreased usage. Yearly echocardiograms showed no cardiac defect or dysfunction, and the aortic annulus and root and pulmonary artery dimensions were consistently within the normal range. Visual acuity remained normal.
In a 9-year-old girl with low muscle mass, growth retardation, and distal arthrogryposis, who also exhibited features of Marfan, Loeys-Dietz, and Beals (121050) syndromes but did not meet the established diagnostic criteria for those syndromes, Rienhoff et al. ... In a 9-year-old girl with low muscle mass, growth retardation, and distal arthrogryposis, who also exhibited features of Marfan, Loeys-Dietz, and Beals (121050) syndromes but did not meet the established diagnostic criteria for those syndromes, Rienhoff et al. (2013) analyzed 6 genes known to be associated with those disorders, including TGFB2 (190220), TGFBR1 (190181), TGFBR2 (190182), SMAD3 (603109), FBN1 (134797), and FBN2 (612570), but found no mutations. Exome sequencing revealed 2 heterozygous de novo changes: 1 was a nonsense mutation in the CDH2 gene (114020); however, Rienhoff et al. (2013) noted that dermal fibroblasts from the patient showed CHD2 levels that were not statistically different from 6 age-matched controls, and that Garcia-Castro et al. (2000) had shown that mice heterozygous for a null mutation in Cdh2 were phenotypically normal at 2 years and muscle mass was not affected. The other variant was a de novo missense mutation in the TGFB3 gene (C409Y; 190230.0003), encoding a nonfunctional TGFB3 ligand. Rienhoff et al. (2013) concluded that the TGFB3 mutation most likely accounted for the clinical findings.