Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Joe Leigh Simpson, Felix De La Cruz, Ronald S. Swerdloff, Carole Samango-Sprouse, Niels E. Skakkebaek, John M. Graham, Terry Hassold, Melissa Aylstock, Heino F.L. Meyer-Bahlburg, Huntingdon F. Willard, Judith G. Hall, Wael Salameh, Kyle Boone, Catherine Staessen, Dan Geschwind, Jay Giedd, Adrian S. Dobs, Alan Rogol, Bonnie Brinton, C. Alvin Paulsen

Research output: Contribution to journalReview articlepeer-review

145 Scopus citations


Purpose: The purpose of this study is to summarize new data on etiology and clinical features of Klinefelter syndrome in order to derive research priorities. Methods: This study was conducted using critical reviews of selective topics, emphasizing less well-recognized clinical findings. Results and conclusions: The phenotype of the prototypic 47,XXY case is well recognized: seminiferous tubule dysgenesis and androgen deficiency. Less well appreciated is the varied expressivity of 47,XXY Klinefelter syndrome, in particular neurological/cognitive perturbations like language and behavioral problems. Effective therapies are available. Reproductive technologies allow 47.XXY men to sire offspring through intracytoplasmic sperm injection (ICSI); however, genetic counseling is complex and success is low. Behavioral and expressive language difficulties are amenable to treatment by androgen therapy and psychological help. Early treatment may be imperative for optimal outcome.

Original languageEnglish (US)
Pages (from-to)460-468
Number of pages9
JournalGenetics in Medicine
Issue number6
StatePublished - Nov 2003


  • Klinefelter syndrome
  • Language
  • Neurocognitive
  • Seminiferous tubules

ASJC Scopus subject areas

  • Genetics(clinical)


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