Trichorhinophalangeal syndrome type I is a malformation syndrome characterized by distinctive craniofacial and skeletal abnormalities and is inherited as an autosomal dominant (Momeni et al., 2000). TRPS I patients have sparse scalp hair, bulbous tip of the nose, ... Trichorhinophalangeal syndrome type I is a malformation syndrome characterized by distinctive craniofacial and skeletal abnormalities and is inherited as an autosomal dominant (Momeni et al., 2000). TRPS I patients have sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature.
Giedion (1966) delineated a syndrome consisting of thin and slowly growing hair, pear-shaped nose with high philtrum, brachyphalangy with deformation of the fingers and wedge-shaped epiphyses. Giedion's patient, a girl, had 2 supernumerary incisors. He found 2 previous ... Giedion (1966) delineated a syndrome consisting of thin and slowly growing hair, pear-shaped nose with high philtrum, brachyphalangy with deformation of the fingers and wedge-shaped epiphyses. Giedion's patient, a girl, had 2 supernumerary incisors. He found 2 previous reports, each describing 2 affected sibs. Furthermore, the parents were consanguineous in 1 case. One of the pairs of affected sibs was reported as pseudo-pseudohypoparathyroidism (van der Werff Ten Bosch, 1959). Hussels (1971) observed affected brother and sister whose parents were not related and allegedly were unaffected, but the father was not available for examination. While showing that in most instances inheritance is autosomal dominant, Giedion et al. (1973) concluded that a recessive form probably exists. Gonadal mosaicism is a frequent phenomenon, however, and it is probably noteworthy that there was so little evidence for a recessive form. Autosomal dominant inheritance seemed unequivocal in light of a family in which affected grandfather, son, and grandson were observed (Murdoch, 1969; McKusick, 1972). The earliest affected male died at age 43 years of a cerebrovascular accident. Beals (1973) described a family in which the father and 2 of 4 children, a male and a female, were affected. Three Japanese families with 19 affected persons in a clear autosomal dominant pedigree pattern were reported by Sugiura et al. (1976). Izumi et al. (2010) reported a 31-year-old man of Native American and Puerto Rican descent who presented with adult-onset chronic joint pain in his neck, back, hips, knees, and ankles. Physical and radiographic examination showed facial and skeletal features consistent with TRPS type 1, and the diagnosis was confirmed by molecular testing. Facial features included low-set, posteriorly rotated ears, prominent malar eminence and orbital ridge, bulbous nose, hypoplastic nasi alae nasi, hypotrichosis, and long philtrum. He also had brachydactyly, wide halluces, and flat arches. Radiographs showed vertebral spondylosis, scoliosis, spondylolisthesis, shortening of the phalanges, osteophyte formation, osteopenia, and secondary arthritic changes. Cone-shaped epiphyses were not observed. Family history revealed that his mother had alopecia and chronic multiple joint pain. The proband had clinical evidence of hypogonadism and mild vitamin D insufficiency, which could contribute to osteopenia, but Izumi et al. (2010) concluded that the skeletal features were secondary to TRPS type 1. The findings suggested that progressive osteopenia and osteoarthritis are part of the phenotype in older patients with TRPS type 1.
Starting from the location of the TRPS1 gene on 8q24, Momeni et al. (2000) positionally cloned a gene that spans the chromosomal breakpoint of 2 patients with TRPS I and was deleted in 5 patients with TRPS I ... Starting from the location of the TRPS1 gene on 8q24, Momeni et al. (2000) positionally cloned a gene that spans the chromosomal breakpoint of 2 patients with TRPS I and was deleted in 5 patients with TRPS I combined with an interstitial deletion. In 10 unrelated patients, Momeni et al. (2000) identified 6 different nonsense mutations in the TRPS1 gene (604386). The findings suggested that haploinsufficiency for this putative transcription factor causes TRPS I. Although Giedion et al. (1973) concluded that a recessive form of TRPS I probably exists, the isolation of TRPS1, a putative transcription factor zinc finger protein that shows its effects in single dose, indicates that haploinsufficiency of this gene causes the condition which, therefore, is inherited as an autosomal dominant. Of the 6 patients in whom mutations were identified by Momeni et al. (2000), 3 were familial and 3 were sporadic; all 6 showed heterozygosity for a mutation. Trichorhinophalangeal syndrome type III (TRPS3; 190351) differs from TRPS I by the presence of severe brachydactyly, due to short metacarpals, and severe short stature. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, Ludecke et al. (2001) performed extensive mutation analysis and evaluated height and degree of brachydactyly in patients with TRPS I or TRPS III. They found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicated that TRPS1 is the major locus for TRPS I and TRPS III. They found no mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the 5 missense mutations altered the GATA DNA-binding zinc finger, and 6 of the 7 unrelated patients with these mutations could be classified as having TRPS III because they had severe brachydactyly, due to short metacarpals, and severe short stature. The data indicated that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.