What are the genetic variants of Klinefelter syndrome?

Updated: Mar 23, 2020
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Variants of Klinefelter syndrome are as follows [32]   [33] :

  • 48,XXYY variant: Patients typically have intellectual challenges (IQ range 60-80, delayed speech, learning disabilities); tall stature (adult height >6 feet); eunuchoid body habitus; sparse body hair; gynecomastia; long, thin legs; hypergonadotropic hypogonadism; and small testes and penis.

  • 48,XXXY variant: Patients typically have intellectual challenges (IQ range 40-60, marked speech delay, slow motor development, poor coordination), average or tall stature, abnormal face (epicanthal folds, ocular hypertelorism, flat nasal bridge), gynecomastia (33-50%), hypergonadotrophic hypogonadism, hypoplastic penis, small testes, fifth-finger clinodactyly, and radioulnar synostosis. 

  • 49,XXXYY: Patients typically have severe intellectual disabilities; passive, but occasionally aggressive, behavior and temper tantrums; tall stature; dysmorphic facial features; gynecomastia; and hypogonadism.

  • 49,XXXXY variant: Males are severely intellectually challenged (IQ range 20-60). Patients have short stature and are microcephalic with dysmorphic facial features (ocular hypertelorism, epicanthal folds, flat nasal bridge, prognathism), and a short or broad neck. Other clinical features include severely impaired language, behavioral problems, low birth weight, cleft palate, gynecomastia (rare), congenital heart defects (patent ductus arteriosus is most common), skeletal anomalies (radioulnar synostosis, genu valgus, pes cavus, fifth-finger clinodactyly), muscular hypotonia, hyperextensible joints, hypergonadotropic hypogonadism, hypoplastic genitalia, and cryptorchidism.

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