Trichorhinophalangeal syndrome type I - Clinical and molecular characterization of 3 members of a family and 1 sporadic case

Background. Trichorhinophalangeal syndrome type I (TRPS I) is a rare autoso mal dominant disorder clinically characterized by sparse and slow-growing h air, pear-shaped nose, elongated philtrum, thin upper lip, and bone deformi ties, in particular, cone-shaped epiphyses of the phalanges. Very recently, the responsible gene TRPS1 has been cloned on human chromosome 8q24. Observation: We describe a mother and her 2 daughters and a female patient with a sporadic case of TRPS I. In the familial case, mutation analysis sho wed an insertional mutation at position 2480 of the TRPS1 gene leading to a premature translational stop. Careful clinical examination showed craniofa cial and radiologic features typical of TRPS I, including short stature, in all 3 affected individuals. Additionally, they presented with a receded tr iangular medio-occipital hairline, which has not been described in TRPS I s o far. In the sporadic case, we identified a single base deletion at positi on 2110 of the TRPS1 gene leading to frameshift and premature translational stop at codon 766. The patient presented with the typical TRPS I phenotype but was of normal stature. Conclusions: The TRPS I is characterized by variable clinical expression of the triad of hair, craniofacial, and skeletal abnormalities. New genetic a pproaches, including mutation analysis, now allow identification of carrier s of the TRPS1 gene mutations.