Purpose: To report a rare case of Down–Klinefelter syndrome associated with bilateral congenital posterior polar cataracts and a novel MAPKAPK3 gene mutation. Methods: A single case was reviewed. Results: A 2-month-old male neonate presented with dysmorphic features, including a flat facial profile, low-set ears, and upslanting palpebral fissures, along with bilateral absence of the red reflex. Ocular examination revealed bilateral congenital posterior polar cataracts. Genetic testing confirmed Down–Klinefelter syndrome (48,XXY,+21) and identified a novel mutation in the MAPK-activated protein kinase 3 gene (MAPKAPK3, c.1039G>A, p.Asp347Asn). While characteristic features of Down syndrome were evident, manifestations of Klinefelter syndrome were not yet apparent owing to the patient’s young age. The patient underwent bilateral pars plana vitrectomy and lensectomy to prevent the development of nystagmus, amblyopia, and strabismus. Conclusions: Down–Klinefelter syndrome (48,XXY,+21) is a rare chromosomal disorder. This case is notable for the coexistence of classic Down syndrome features, genomic confirmation of Klinefelter syndrome, and a previously unreported MAPKAPK3 mutation. Close and long-term follow-up will be essential to understand the clinical implications of this unique genetic combination.
Arias-González et al. (Sat,) studied this question.