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Asian Journal of Andrology (2010) 12: 561-566. doi: 10.1038/aja.2010.6; published online 22 March 2010.
Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis
Amrit Bhangoo1,*, Francoise Paris2,*, Pascal Philibert2, Francoise Audran2, Svetlana Ten1 and Charles Sultan2
1 Pediatric Endocrinology Division of Maimonides Infants and Children's Hospital of Brooklyn, Children's Hospital at SUNY Downstate, Brooklyn, NY 11219, USA
2 Endocrine Service, Hôpital Lapeyronie, Central University Hospital of Montpellier, 34295 Montpellier cedex 5, France
Correspondence: Prof. Charles Sultan, Endocrine Service, Hôpital Lapeyronie, Central University Hospital of Montpellier, 191 avenue Doyen Gaston Giraud, 34295 Montpellier cedex 5, France. Fax: +33-04-6704-8573 E-mail: c-sultan@chu-montpellier.fr
* These two authors contributed equally to this work.
Received 27 November 2009; Accepted 27 January 2010; Published online 22 March 2010.
| Abstract |
Partial androgen insensitivity syndrome (PAIS) is the milder variant of androgen receptor (AR) defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-α reductase type 2 (SRD5A2) deficiency. We describe two cases of isolated micropenis: one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin (hCG) stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone (T) level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family.
Keywords: androgen receptor; gynecomastia; isolated micropenis; male infertility |
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