ESPE Abstracts

Objectives: Trichorinophalangeal syndrome (TRPS) is a cause of syndromic short stature; and is characterized by typical dysmorphology, ectodermal dysplasia, and skeletal findings. There are two types of TRPS; TRPS-I caused by monoallelic pathogenic variants in the TRPS1 gene, and TRPS-II caused by whole gene deletion. TRPS-II; also called Langer-Giedion Syndrome (LGS), in which multiple exocytoses can be seen in addition to typical TRPS features due to contagious deletion of the EXT1 gene at the same chromosomal region. Here we describe an 8 years old girl with LGS, who also had anal atresia and vertebral fusion defects.

Case: An 8 years old girl was referred for short stature. She was born to unrelated parents at term with a birth weight of 3000 gr (-0.8 SDS). At 15 days of age, she had an operation for anal atresia. She began to walk at 24 months old, and talk at 30 months old. On her initial examination height SDS was -2.12 (113.7 cm), weight SDS was -2.04 (18kg). She was noted to have large-pronounced ears, a bulbous tip of the nose, broad nasal root, hypoplastic alae nasi, long philtrum, fine and sparse hair, broad eyebrows, brachydactyly, short 5th metacarpal, pes planus, umbilical hernia, scoliosis, and multiple exocytoses. In addition imaging examinations revealed multiple exocytoses in long bones, costae, and pelvic bones; osteopenia in lateral vertebral radiograph; ivory epiphysis and cone-shaped epiphysis in phalanges, short metacarpals of the fifth finger, fusion anomaly in cervical-thoracic vertebrae and costal malalignment. LGS was considered in the etiology and a contiguous 10.14 Mb deletion involving 8q23.3-q24.12 was detected by array comparative genomic hybridization, leading to haploinsufficiency of TRPS1, RAD21, and EXT1 genes.

Conclusions: Patients with LGS show clinical variability depending on the loss of genes in the deleted region. To date renal defects, ventricular septal defects persistent cloaca, prune belly, and annular pancreas have been described in several patients. Besides growth hormone deficiency, corpus callosum agenesis and hypothyroidism were previously reported in a few cases. Interestingly, our patient was found to have anal atresia and vertebral fusion defects which, to our knowledge, is a novel co-existing feature in patients with TRPS II. Our patient broadens the spectrum of disease, further description of these cases will highlight the genes responsible for additional clinical manifestations of the disease.