Trichorhinophalangeal syndrome type I: clinical and molecular characterization of 3 members of a family and 1 sporadic case
Seitz, C.S.; Lüdecke, H.J.; Wagner, N.; Bröcker, E.B.; Hamm, H.
Archives of Dermatology 137(11): 1437-1442
2001
ISSN/ISBN: 0003-987X PMID: 11708946 Document Number: 530059
Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant disorder clinically characterized by sparse and slow-growing hair, pear-shaped nose, elongated philtrum, thin upper lip, and bone deformities, in particular, cone-shaped epiphyses of the phalanges. Very recently, the responsible gene TRPS1 has been cloned on human chromosome 8q24. 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 showed an insertional mutation at position 2480 of the TRPS1 gene leading to a premature translational stop. Careful clinical examination showed craniofacial and radiologic features typical of TRPS I, including short stature, in all 3 affected individuals. Additionally, they presented with a receded triangular medio-occipital hairline, which has not been described in TRPS I so far. In the sporadic case, we identified a single base deletion at position 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. The TRPS I is characterized by variable clinical expression of the triad of hair, craniofacial, and skeletal abnormalities. New genetic approaches, including mutation analysis, now allow identification of carriers of the TRPS1 gene mutations.