Endocrine Abstracts

Introduction

Werner syndrome (WS) is a rare genetic disorder that displays clinical features suggestive of accelerated aging. Also known as adult progeria, it is caused by mutations in the WRN gene, which encodes a RecQ DNA helicase. Primary characteristics of this syndrome are progeroid changes of hair, bilateral cataract, atrophic skin, soft-tissue calcification, bird-like face, abnormal voice and many others features. Here we report 5 patients that presented with different phenotypes of this syndrome showing the heterogenicity of this genetic disorder.

Case report

All of our 5 patients were born from consanguineous parents. The first 2 patients are brother and sister. The older sister was 22-year-old and followed for short stature and hypogonadism. She had a bird-like face with an atrophic skin. She developed over the years bilateral cataract and adrenal insufficiency. She was treated with hormonal replacement therapy and hydrocortisone. As for her brother, the diagnosis of WS was evoked at the age of 10, when he consulted for short stature and bird-like face. A hypothyroidism and adrenal insufficiency were also diagnosed later. The second family consist of 2 brothers aged 34 and 32, who consulted for short stature, hypogonadism and hypothyroidism. Both presented with pinched facial appearance, pitched voice, skin atrophy, diabetes mellitus (DM), dyslipidemia and cataract. And the last patient, is 36-year-old male patient who was first followed for hypothyroidism and DM. Considering the association with hypogonadism, short stature and atypical facial features, the WS was probable. All the 5 patients were treated with hormonal replacement to compensate for the different deficiencies. Unfortunately, the genetics test was not available to confirm this disorder.

Conclusion

WS is a rare syndrome but it must be evoked, considering its association with different malignancies such as thyroid follicular carcinomas, malignant melanoma, meningioma, soft tissue sarcomas, primary bone tumors and leukemia. They also develop premature atherosclerosis, which is the second cause of death for those patients. The discordances between the signs and the age of diagnosis may be attributed to numerous factors, such as differential expressions and regulations of the WRN protein in various cell types and tissues, rates of cell turnover, and variations in the replicative potentials of various types of stem cells. The role of the genetic tests is becoming more and more necessary to unsure the proper diagnosis and to eventually lead a standard follow-up of the different comorbidities.