Beyond the X's and Z's: Sleep disorders in Klinefelter syndrome from case report to cohort and literature review

Abstract

Study objectives: Klinefelter syndrome (KS) is a genetic disorder characterized by hypogonadism and hormone imbalances. The coexistence of sleep disorders in the setting of Klinefelter syndrome is relatively unexplored in literature, highlighting the need for better understanding.

Methods: We reviewed the case of a 29-year-old male with Klinefelter syndrome, sleep disruption, and an abnormal overnight oximetry. This case prompted a retrospective chart review of patients with KS seen at our institution since 2000, as well as a review of the literature of sleep disorders in Klinefelter syndrome.

Results: We identified that nearly one-third of confirmed patients with KS had either confirmed or suspected Obstructive Sleep Apnea (OSA), a markedly higher prevalence than reported in the general population. Additionally, although the prevalence of Central Sleep Apnea (CSA) in KS in our series was similar to that of the general population, its occurrence in the absence of typical risk factors suggests a predisposition to idiopathic CSA. Although circadian rhythm disorders have been described in individual reports, our review did not identify many cases, implying that these disorders may be underrecognized or less commonly documented in routine care.

Conclusions: The prevalence of presumed idiopathic CSA in confirmed patients with KS raises the possibility of KS-specific mechanisms of ventilatory control instability. Importantly, three-quarters of patients with KS with documented sleep complaints had no formal sleep medicine evaluation, underscoring a gap in structured assessment. This may be secondary to constraints surrounding access or referral bias, and bears further evaluation.

Keywords: Central sleep apnea; Klinefelter; Melatonin; Sleep disturbance; Testosterone.