Genetics / Syndromes

Question 1

What are the clinical manifestations of Klinefelter syndrome?

Answer 1

Cognitive development

• Most people have normal intelligence
• Learning disabilities, autism, social problems

Fertility/ puberty

• Primary hypogonadism, infertility, azoospermia

Cardiac

• 55% have mitral valve prolapse

Oncology

• Increased frequency of extragonadal germ cell tumours
• Carcinoma of the breast is 20 times more frequent

Growth + body habitus

• Eunuchoid body habitus: tall, US:LS ratio is decreased + long arm span
• Clinodactyly

Prognosis

• Increased morbidity later in life from pulmonary disease, cancers, diabetes, SLE

Question 2

Investigations + Management for Klienfelter

Answer 2

Investigations

• Karyotype, microarray

Management

• Testosterone, LH + FSH levels @ 11-12 years
  
  • Testosterone replacement one LF + FSH begin to rise above normal
• Screen for complications
  
  • DEXA
  • Fasting BSL, lipids, HbA1c (at risk of metabolic syndrome)
• Aromatase inhibitors: treatment of gynaecomastia