Endocrine Abstracts

Introduction: The 48XXXY karyotype is an infrequent (incidence about 1/50000 male births) sporadic aneuploidy of the sex chromosomes, classically considered as a variant of the Klinefelter syndrome (47XXY). Although many of their characteristics are shared, patients with the 48XXXY karyotype suffer from additional endocrinological and neuropsychological disturbances which are not part of the classic Klinefelter syndrome. Hereby we present a clinical case.

Methods: Review of the patient’s clinical records and of the relevant literature.

Case Presentation: A male, 27 year old patient, previously diagnosed of left renal agenesis, hypertriglyceridemia and cognitive impairment of unknown etiology with a 66% legal disability was referred to our Endocrinology Clinic from the Urology Dept, for workup of testosterone deficiency. He had undergone a standard vasectomy, but his testicles were reported as partially atrophic and his total testosterone was 0.96 ng/ml (normal range 2.8 - 10.7 ng/ml). The anamnesis disclosed cognitive impairment since childhood, with speech development at the age of 4 years and enuresis until 12 years. Growth was normal, having reached target adult height, and the development of secondary sexual characters was normal except for absence of facial hair. The patient had normal erections and maintained regular sexual activity. The physical examination disclosed dysmorphic facial features, bilateral gynecomastia, penis of normal size, testicular volume of 10-12 mL, scarce pubic and axillary hair, gynecoid fat distribution, short trunk with long limbs and bilateral cubitus valgus. Lab tests were compatible with hypergonadotropic hypogonadism, with total testosterone 0.82 ng/ml, FSH 36 mU/ml and LH 24 mU/ml. The workup was completed by the karyotype 48XXXY.

Conclusions: Some of the peculiarities of our patient, such as cognitive impairment, genital hypoplasia and dysmorphic features are characteristic of the 48XXXY syndrome, while others such as unilateral renal agenesis are less often associated with it. Other developmental abnormalities involving the cardiac, neurological and genitourinary systems may be present. This case underscores the heterogeneity of the syndrome. The early diagnosis of the 48XXXY syndrome is highly desirable because it is significantly more complex than the classic Klinefelter syndrome (47XXY) with additional somatic and cognitive disturbances, and usually requires multidisciplinary care and follow-up.