Endocrine Abstracts

Introduction: Double aneuploidies are extremely rare. Klinefelter syndrome is a chromosomal disorder characterized by an extra X chromosome in male cells - approximately 80% are 47,XXY; the remaining 20% are mosaic 47,XXY/46,XY. Down syndrome is caused by trisomy of chromosome 21. The prevalence of Klinefelter syndrome is approximately 1 to 2.5 per 1000 boys and men (0.1 to 0.25 percent). The incidence of Down syndrome is approximately 1 in every 990 live births across Europe (10.1 per 10,000 live births). Both chromosomal abnormalities rarely occur together; calculated incidence is 0.4-0.9 per 10000 male newborn. Patients with Down syndrome exhibit characteristic features at birth, while features of Klinefelter syndrome might not be apparent until puberty. Typical Klinefelter syndrome clinical features are tall stature with long extremities, small testes, and learning disabilities. Patients with Klinefelter syndrome have impaired gonadal function resulting in testicular atrophy and hypergonadotropic hypogonadism and azoospermia.

Case presentation: The phenotypic characteristics of a 28-year old man showed the presence of features of Down syndrome. The family had no known history of chromosomal abnormalities or other syndromes. At first visit to pediatrician he presented with midfacial hypoplasia and dermatologic disorders (folliculitis), but without accompanying congenital heart defects, hypothyroidism, diabetes or renal disease. During follow-up, he presented decreased bone mineral density, normal body weight and height, and gastroesophageal reflux disease. He had a global developmental delay, small testes by age 12. At the age of 13 he started testosterone treatment with 1000 mg testosterone undecanoate/3 months and supplementation with vitamin D and calcium. Five years later testosterone dose was decreased to 750 mg/3 months because of the worsening skin inflammation. At the age of 25 he was transitioned to adult endocrinologist. Following the altered behavior as a side effect of testosterone therapy in spite of normal serum testosterone concentrations, his therapy was switched to transdermal testosterone. Examinations within the last 12 months show that the patient has not developed diabetes, cardiovascular or autoimmune complications. Thyroid function is normal, abdominal ultrasoud showed hepatic steatosis, cardiologist reported no abnormalities.

Conclusions: Double aneuploidy with Down-Klinefelter syndrome, as seen in our case, usually presents in the neonatal period with the clinical features of Down syndrome, while features characteristic of Klinefelter syndrome appear later. Both aneuploidies have a potential to weaken or enhance each other. In the presence of typical features of Down syndrome, we highly recommend proceeding with chromosomal analysis.