Clinical and molecular characterization of a patient with Tricho-rhino-phalangeal syndrome (TRPS) and growth hormone (GH) deficiency

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 596-630-Pediatric Endocrinology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-607
Sharona Azriel Sr.*1, Guiomar Perez de Nanclares2 and Arrate Pereda3
1Hospital Infanta Sofia, Madrid, Spain, 2Hospital de Txagorritxu, Vitoria-Gasteiz, Spain, 3Hospital Txagorritxu, Vitoria, Spain
Background: TRPS is a rare genetic disease characterized by craniofacial and skeletal abnormalities, an autosomal dominant disorder, due to mutations in the TRPS1 gene localized in 8q23.3. TRPS is classified in 3 types with striking features: sparse, slowly growing scalp hair, laterally sparse eyebrows, a bulbous tip of the nose, long flat philtrum, thin upper vermillion border, protruding ears, brachydactyly, short stature, cone-shaped epiphyses, hip malformations (coxa plana, coxa magna or coxa vara) and intellectual disability.

Clinical Case: A 31 year old woman was referred to endocrine clinic for obesity. Her facial features, brachydactyly, shortening of II-V metacarpals and middle phalanges, short stature (-4DS), biochemical abnormalities confirmed (mildly elevated serum parathyroid with normal 25-OH-vitamin levels, low normal calcaemia) and GH deficiency with diminished response in 2 stimulation tests and low IGF-1 levels, maked us suspected pseudohypoparathyroidism type Ia, with presence of Albright's osteodystrophy's phenotype. We were unable to identify any genetic and epigenetic alterations at GNAS locus. Subsequently all exons of the TRPS1 gene were analyzed from genomic DNA and the analysis showed p.Arg944fsGly*3 mutation in heterocygous. The genetic study confirmed the diagnosis of TRPS. The pronounced shortening metacarpals and metatarsals and the short stature of the patient guide to TRPS type III.

Conclusion: TRPS should be considered in the differential diagnosis of other inherited diseases coursing with short stature, and brachydactyly and GH deficiency. Cone-shape epiphyseal radiologic changes are pathognomonic of TRPS. Calciotropic axis alterations have not been described so far in the TRPS. Genetic counselling is mandatory due to de AD inheritance, as well as the screening for cardiopathies, kidney diseases and hip osteonecrosis, often present in this syndrome

Nothing to Disclose: SA Sr., GP, AP

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