Background: 48,XXYY syndrome is a rare chromosomal anomaly that causes infertility, developmental and behavioral disorders, among other health problems, in males. Affected patients are often taller than other males of their age. This condition is not inherited; it is predicted to occur as a random event during gametogenesis and is estimated to affect 1 in 18,000 to 40,000 males. Clinical case: A 8.7-year-old male patient was brought by his parents who reported a history of learning disabilities, mainly on math, as well as poor coordination and disabled motor skills, despite good visual-spatial skills and memorization. He has been followed by a neurologist and a karyotype required as part of the neurological investigation showed 48,XXYY aneuploidy. The patient was born after a full-term pregnancy resultant from in vitrofertilization. At birth, height and weight were appropriate for gestational age. He had normal motor development (started crawling at 8 months and walking at 14 months), but delayed development of the speech (3.4 years-old). He also had delayed appearance of the primary teeth. Previous pathological history included asthma and myopia, without additional comorbidities. At the first evaluation at the Endocrine Unit he had normal weight (33.2 Kg; Z: +1.29), but an elevated height for age (144.5 cm; Z: +2.34). His bone age showed an asynchrony between carpal and phalanxes (6 years and 9 years, respectively), as evaluated by the Greulich-Pyle method. Misaligned teeth and long fingers were also noted. A normal appearing external male genitalia was seen, while testicular volume was slightly higher than expected for his chronological and bone age (Tanner stage G2P1; Right and left testis of 4mL). Biochemical exams and thyroid function tests were unremarkable, and hormonal blood exams performed at the age of 9 year and 1 month were compatible with initiation of pubertal development as was his Tanner stage: LH 0.52 mIU/mL (prepubertal reference < 0.3), FSH 5.4 mIU/mL, Total Testosterone 28.04 ng/dL, Estradiol 16.4 pg/mL, all by a immunochemiluminescent assay. Echocardiogram was normal, as well as MRI of the brain. The patient continues to be followed by a multidisciplinary team in order to address all the aspects of the syndrome, including neurological, behavioral and cognitive function, and its endocrine hallmarks, particularly growth pattern, osteometabolic status, pubertal development and sexual hormones production in later life. Conclusion: We report a rare case of 48,XXYY syndrome, with a slightly early pubertal development and asynchronous bone age maturation. Close follow up is warranted in those challenging cases due to the potential impact on multiple health aspects.
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