We describe the case of a rare variant of Klinefelter's syndrome with a 49 XXXXY karyotype. This rare form was first described in 1960 and has sufficiently distinctive features (compared with the classic 47 XXY karyotype) to be detected in childhood. Relevant features are compared with those described elsewhere in the literature. Case ReportA two-year, four-month-old Saudi male was referred to Suleimania Children's Hospital, Riyadh, because of recurrent chest infections and questionable immune deficiency.Past history revealed the child was born after an eight-month pregnancy with a low birth weight (1.5 kg), followed by delayed milestones (smiled at five months, sat at eighteen months, walked at two years, three months) and delayed speech. He exhibited emotional lability (cried very easily), had had recurrent chest infections, and had had conjunctivitis since six months of age.The parents were not related; the mother was 35 years old, and the father, 60 years. The seven siblings were normal and healthy.Growth parameters showed a height below 1.75 -SD, weight below 1 -SD, and normal head circumference. Examination revealed an immature-looking child showing delayed development, who showed abnormal features such as short neck, upward slanting palpebral fissures, hypertelorism, epicanthal folds, broad nose, kyphosis, and short incurved fifth finger. Other relevant features included limited elbow pronation, a soft systolic murmur with a loud second sound, and abnormal external genitalia with a very small phallus, undescended small atrophic testes, hypoplastic scrotum, and coronal hypospadias.Routine blood analysis (complete blood count, erythrocyte sedimentation rate, blood urea nitrogen, blood glucose, electrolytes) and urine test results were all normal. Tuberculin test (10 TU) was negative. Immunoglobulin assays showed normal IgG and IgM, and low IgA. IgG subclasses and cellular and nonspecific immunity were not evaluated. Hormonal blood assays showed a low testosterone level of 0.01 ng/ml (reference interval, 2.4-10.9 ng/ml) with a high follicle stimulating hormone (FSH) level of 31.1 IU/L (reference interval, 1.9-2 IU/L) and normal luteinizing (LH) hormone level of 3.2 mIU/ml (reference interval, 3.13-5 mIU/ml). Human chorionic gonadotropin (HCG) test showed a poor testosterone response (0.09 ng/ml). Lutenizing hormone releasing hormone (LHRH) showed a high FSH response, more so than the LH response. Chromosomal analysis showed a 49 XXXXY karyotype. Electrocardiogram revealed a relatively low-voltage, single ventricular extra systole. Ultrasound examination of the abdomen, echocardiogram, and computed tomographic scan of the brain (previously done in a local hospital) were normal. Skeletal survey showed delayed bone age (1 year), kyphosis, short incurved fifth finger, radioulnar synostosis, shallow acetabulum, and mild right hip dislocation. Chest x-ray study showed mild cardiomegaly. Based on these findings, Klinefelter's syndrome, rare variant 49 XXXXY, was diagnosed. The patient was managed symptomatically an...