Endocrine Abstracts (2010) 24 BC1.4

Lessons from Klinefelter syndrome (47,XXY): a common DSD but with significant variation in presentation

J S Gopal-K1, L Patel1, S Ehtisham1, R Amin1, S Hennayake3, I Banerjee1, P E Clayton2 & M S Skae1


1Department of Paediatric Endocrinology, Royal Manchester Childrens Hospital, Manchester, UK; 2Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK; 3Department of Paediatric Urology, Royal Manchester Childrens Hospital, Manchester, UK.


Background: Klinefelter syndrome (KS) is the commonest sex chromosomal disorder. Characteristic features include male phenotype with hypogonadism and progressive testicular failure, gynaecomastia and learning difficulties. The association between mediastinal germ cell tumours (GCT-M) and KS is well established, with KS occurring in 20% of GCT-M patients and the reported incidence of GCT-M in KS being 1.5 per 1000 (Nichols, 1991). Genital anomalies are also known to be rarely observed in KS (Lee et al., 2007).

We report two unusual presentations of KS.

Case 1: A baby, with an antenatal diagnosis of KS (47, XXY), was born to non-consanguineous parents with normal female genitalia showing no evidence of clitoromegaly, labial fusion or palpable gonads, with separate urethral and vaginal openings. Antenatal counselling had prepared parents for a male infant. A poor testosterone response to HCG stimulation, low anti-mullerian hormone and markedly elevated gonadotrophins were consistent with gonadal dysgenesis. Postnatal karyotyping confirmed 47, XXY with preservation of the SRY gene.

Case 2: An 8-year-old boy presented with precocious puberty and severe virilisation. Investigations included a suppressed GnRH (peak LH & FSH 0.6 IU/L), raised serum testosterone (9.2 nmol/L), β-HCG levels (24 U/L) and alpha fetoprotein (90 IU/L). A GCT-M was detected on CT-imaging. The tumour was successfully surgically resected and treated with chemotherapy. Significant behavioural outbursts 22 months after treatment prompted karyotype screening confirming a diagnosis of KS in the patient retrospectively.

Conclusions: These cases demonstrate the diversity of the KS phenotype. In antenatally diagnosed KS, clinicians must be mindful that abnormal genitalia should be included in the possible phenotypic features described in the condition. Screening for β-HCG secreting tumours is also essential in KS children presenting with early/precocious puberty. We also recommend early karyotype screening in children with a diagnosis of GCT-M to exclude associated KS.

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