METABOLIC BONE DISEASE AND FRACTURE RISK IN ROTHMUND-THOMSON SYNDROME

Abstract

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis disorder. It is characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, juvenile cataract, increased risk of osteosarcoma, decreased bone mass, and predisposition to certain cancers particularly certain types of skin and bone cancer in addition to associated with diminished bone mineral density. In childhood, the inflammation tends to affected skin area develops into a more chronic pattern of rash called as poikiloderma, characterized by telangiectases; small spots of atrophy; and abnormal skin areas pigmentation alternating between hyperpigmentation and hypopigmentation, giving a lacy, web-like, or mottled appearance. Skin manifestations that to be more prominent in adulthood is called hyperkeratosis, where certain areas of body like palms and soles, knees and around the fingers or toes, become thickened and overgrown and develop a rough, wart-like texture. In study we have reported that a majority of patients with RTS having some skeletal abnormalities like radial aplasia or hypoplasia, synostoses, abnormal metaphyseal trabeculation, brachymesophalangy, and patellar defects. In addition osteopenia, pathologic fractures, and delayed fracture healing have also been founded; it may lead to a more systemic skeletal involvement. Material and method: The present study was conducted in the Dept. of Ortho at Govt. Medical College and Shri Vinoba Bhave Civil Hospital, Silvassa. Total 35 patients with RTS were included in this study (22 males, 13 females). The study includes children (23 mean ages was 5.94 ± 1.34) and adults (12 mean ages was 35.98 ± 6.87). Radiographs were reviewed by two radiologists. From the patients and their relative family history were taken and pedigree was constructed for each kindred.  Peripheral blood samples and skin punch biopsy samples were obtained from each patient. Skin biopsy samples were transported in -modified Eagle medium (-MEM) with 10% fetal bovine serum (Invitrogen, Carlsbad, CA). Blood samples obtained in acid– citrate–dextrose collection tubes were used to establish Epstein– Barr virus-transformed lymphoblastoid cell lines (LCLs). Result: Total 35 patients were included in this study with RTS 24 males and 11 females.  The study includes children (23 mean ages was 5.94 ± 1.34) and adults (12 mean ages was 35.98 ± 6.87).  Twenty three had pathogenic variants in alleles of RECQL4 and twelve had no detectable pathogenic variants (Type 1 RTS: n = 12). The median age in this sub study (8 males, 5 females) was 10years (range 1–49 years). Eight patients who participated in calcium kinetic studies DXA scans were performed.  The median whole body aBMD-for-age Z-score in these individuals was 1.3 (IQR 0.9 to 1.4) and median lumbar spine aBMD-for-age Z-score was 2.5 (IQR 0.2 to 3.1). EP and V0þ were found to be within the age-adjusted normal ranges for all patients. Conclusion: Rothmund-Thomson syndrome is a rare autosomal recessive disorder in most common which is characterized by particularly radial ray defects and imaging by dental and skeletal abnormalities. In RTS patients with mutations in RECQL4 gene skeletal abnormalities are very common and skeletal abnormalities are also increased risk for pathologic fragility fractures. Due to associated diminished bone mineral density there will be delayed fracture healing. Hence RTS patients with the RECQL4 gene mutation are also high risk of developing osteosarcoma which could be present as a pathologic fracture. Therefore attention should be made for underlying malignancy in all fractures occurring in RTS patients.

Keywords: Rothmund-Thomson syndrome (RTS), Osteosarcoma, RECQL4, Poikiloderma.