title: Isolated 'idiopathic' micropenis: hidden genetic defects?
abstract: Micropenis is defined as a stretched penile length of less than 2-2.5SD for age. Aetiologies include hypogonadotropic hypogonadism, testicular dysgenesis, defects in testosterone synthesis, androgen resistance [5α-reductase (5αR) deficiency or partial androgen insensitivity] and other rare causes like growth hormone GH deficiency. Often, the cause remains unknown. The aim of this study was to determine whether isolated micropenis with normal plasma testosterone could hide a molecular defect in the androgen pathway. Twenty-six boys with isolated micropenis were included in this study. All of them had 46,XY karyotype, normal luteinizing hormone and follicle-stimulating hormone and a normal plasma testosterone response to human chorionic gonadotropin testing. Androgen receptor (AR), 5αR and steroidogenic factor 1 (SF1) genes were sequenced. A mutation in the AR gene was found in two patients, and a new mutation in the SF1 gene was found in one patient who was the only one to have a low level of inhibin B (InhB). This is the first report of isolated micropenis as a revealing symptom of AR and SF1 mutations. Anti-Mullerian hormone and InhB should thus be evaluated in patients with isolated micropenis, even when plasma testosterone is in the normal range. Detection of gene mutations is helpful for diagnosis, treatment and genetic counselling for probands.
authors.affiliation: Unité d'Endocrinologie Pédiatrique, Hôpital Arnaud de Villeneuve, CHU Montpellier, Montpellier Cedex 5, France.
authors.forename: F
authors.initials: F
authors.lastname: Paris
authors.forename: K
authors.initials: K
authors.lastname: De Ferran
authors.forename: A
authors.initials: A
authors.lastname: Bhangoo
authors.forename: S
authors.initials: S
authors.lastname: Ten
authors.forename: N
authors.initials: N
authors.lastname: Lahlou
authors.forename: F
authors.initials: F
authors.lastname: Audran
authors.forename: N
authors.initials: N
authors.lastname: Servant
authors.forename: F
authors.initials: F
authors.lastname: Poulat
authors.forename: P
authors.initials: P
authors.lastname: Philibert
authors.forename: C
authors.initials: C
authors.lastname: Sultan
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D005640:Follicle Stimulating Hormone / Q000097:blood; D005832:Genital Diseases, Male / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010413:Penis / Q000002:abnormalities; D017386:Sequence Homology, Amino Acid; D054339:Steroidogenic Factor 1 / Q000737:chemistry / Q000235:genetics; D013739:Testosterone / Q000097:blood
chemical_list: C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone