Pentasomy 49,XXXXY syndrome: Case report

Abstract

Pentasomy 49,XXXXY is a rare sex chromosome polysomy, clinically expressed as a combination of mental retardation, facial dysmorphism, and genital, cardiac and skeletal malformations. The incidence of the condition is estimated to be 1 in 85,000 male births. It was originally described by Fraccaro and colleagues in 1960. A 5-year-old boy who was noticed to have a small penis and facial dysmorphism was referred for genetics studies. He was the first baby born to a nonconsanguineous couple. The birth weight was 2,500 g. The examination findings were: small frontal and occipital asymmetry, upslanted palpebral fissures, hypertelorism, flat nasal bridge, board neck, bilateral clinodactyly, mild mental retardation and small penis (both testes were in well-formed scrotal sacs). No cardiovascular alterations were detected. Chromosome culture and karyotyping were performed using standard techniques and showed a karyotype of 49,XXXXY. Although initially 49,XXXXY pentasomy was considered a variant of Klinefelter syndrome, it is currently recognized as a separate clinical entity distinguished by facial features, multiple skeletal and cardiac defects, and short stature. A 49,XXXXY karyotype is thought to arise from maternal nondisjunction which occurs during both meiosis I and meiosis II. This produces a secondary oocyte with four X chromosomes, which, when fertilized by a Y chromosome-bearing sperm, results in an embryo with 49,XXXXY syndrome. In this case, the facial dysmorphism and small penis were the main features which led to a suspicion of sex chromosome aneuploidy that was confirmed by chromosomal analysis. The prognosis of these children depends on the extent of severity of the condition, while the management mandates a multidisciplinary approach with pediatric endocrinology, pediatric surgery, orthopedics, psychiatry and clinical genetics evaluation.