Endocrine Abstracts

Back ground

49, XXXXY syndrome is a rare defect of sex chromosomes frequently considered as a variant of Klinefelter syndrome. It is often associated with more severe dysmorphic features, hypogonadism, mental retardation, musculoskeletal abnormality, and rarely with diabetes mellitus due to insulin resistance.

The goal: To describe clinical, biochemical, hormonal, radiological and developmental status of the patient with 49, XXXXY karyotype.

Report of the patient

22 years old male referred because of tall stature, sexual perversion with underdeveloped genitalia and poor scholastic performance. The patient was born by caesarean section, weight 2500 g, no history of hypoglycaemia or jaundice. He had delayed mile stone of development. He had normal height as per his fellow peer till the age of 15 yrs followed by rapid increase in height after that.

Physical examination

Revealed acanthosis nigricans with skin tag. Height 180 cm, Weight–80 Kg, BMI 24.7 height/m² with Arm Span of 183 cm, B/l, Testis of 2 ml size and Stretched Penile Length–6 cm, tanner stage 1, mid parental height - 164.75 cm, Upper Segment–80 cm, Lower Segment–100 cm with US: LS ratio 0.8. There was broad forehead and nasal bridge, hypertelorism, epicanthic folds, low set ears, pes cavus, deformity of left elbow joint, genu valgum, clinodactyly, small 4th, 5th toes.Psycho-cognitive development was retarded. Binet Kamat test of intelligence showed IQ of 45 (moderate mental retardation), behavioural problems with articulation difficulties. A chromosome study revealed the 49, XXXXY karyotype.

On radiographic examination

X-rays -hand and wrist- Delayed bone age with incomplete closure of growth plate. MRI of cranio-vertebral junction showed increased Atlanta-dental interval, suggestive of Atlanta-axial instability.

Biochemical tests

Metabolically, he had insulin Resistance, with fasting insulin 65.29 m U/l & FBS–112 mg/dl with HOMA-IR score of 18.1. His FBS 126 mg⁵, PPBS 145 mg% with A1c 8.1%. Serum testosterone was 14.8ng/dl, LH 17.86 mIU/ml, FSH 19.79 indicating hypergonadotropic hypogonadism.

Medical advice

He was stared metformin 500 mg twice daily with life style modification in the form of diet and exercise. Testosterone injection 100 mg im was started. A clinical psychologist consultation was taken for behavioural therapy and parental counselling.

Conclusion

Patient with 49, XXXXY karyotype needs proper hormonal, psychiatric, appropriate skeletal, and cardiological evaluation. Early detection of deficit allows starting early intervention, parallel to behavioural and cognitive therapy, to support adequate management of this syndromic subject.