Micropenis

Abstract: A micropenis is an abnormally small penis with a normal configuration. This finding constitues a sign not a diagnosis. The etiologies may be classified as hypogonadotropic hypogonadism, primary hypogonadism, androgen insensitivity, or idiopathic; among 45 patients, the respective percentages in these categories were 31, 24, 2 and 7% with 36% as yet undiagnosed. Various clinical syndromes may include a micropenis and can be classified in one of the etiologic categories. This paper provides the criteria for determining the presence of a micropenis. A phallic length which is 2.5 or more standard deviations below the mean should be considered as abnormal; for an infant of 0 to 5 months of age, the lower limit is 1.9 cm. The technique of penile measurement, determination of etiology, guidelines for sex of rearing and psychologic, surgical and medical management are discussed.

Abstract: Conversion of testosterone (T) to dihydrotestosterone (DHT) in genital tissue is catalysed by the enzyme 5 alpha-reductase 2, which is encoded by the SRD5A2 gene. The potent androgen DHT is required for full masculinization of the external genitalia. Mutations of the SRD5A2 gene inhibit enzyme activity, diminish DHT formation, and hence cause masculinization defects of varying degree. The classical syndrome, formerly described as pseudovaginal perineoscrotal hypospadias, is characterized by a predominantly female phenotype at birth and significant virilization without gynecomastia at puberty. We investigated nine patients with steroid 5 alpha-reductase 2 deficiency (SRD). Phenotypes, which were classified according to the severity of the masculinization defect, varied between completely female (SRD type 5), predominantly female (SRD type 4), ambiguous (SRD type 3), predominantly male with micropenis and hypospadias (SRD type 2), and completely male without overt signs of undermasculinization (SRD type 1). T/DHT-ratios were highly increased ( > 50) in the classical syndrome (SRD type 5), but variable in the less severe affected patients (SRD types 1-4) (14-35). Mutations in the SRD5A2 gene had been characterized using PCR-SSCP analysis and direct DNA sequencing. A small deletion was encountered in two patients, while all other patients had single base mutations which result in amino acid substitutions. We conclude that phenotypes may vary widely in patients with SRD5A2 gene mutations spanning the whole range from completely female to normal male without distinctive clinical signs of the disease. Hence, steroid 5 alpha-reductase deficiency should be considered not only in sex reversed patients with female or ambiguous phenotypes, but also in those with mild symptoms of undermasculinization as encountered in patients with hypospadias and/or micropenis. A classification based on the severity of the masculinization defect may be used for correlation of phenotypes with enzyme activities and genotypes, and for comparisons of phenotypes between different patients as the basis for clinical decisions to be made in patients with pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.

Abstract: Context: A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. Objective: The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes. Design, Setting, and Subjects: This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center. Main Outcome Measures: History of spontaneous fertility, regular menses, testicular growth, or normalization of serum sex steroids, LH secretory profiles, brain imaging findings, and sequences of 14 genes associated with IHH were reviewed. Results: Of 308 patients with IHH, 44 underwent reversal. Time-to-event analysis estimated a lifetime incidence of reversal of 22%. There were no differences in the rates of cryptorchidism, micropenis, or partial p...

Abstract: We describe 2 karyotypically male infants with terminal deletion of 10q and mental retardation, multiple phenotypic anomalies and abnormal genitalia. One [karyotype 46,XY,del(10)(q26.1)] had female external genitalia; the other [karyotype 46,XY,−10,+der(10)t(10;16)(q26.2;q21)] had an intersex phenotype. Of 8 males previously reported with terminal 10q deletion as the major or only cytogenetic abnormality, 2 had on intersex phenotype, and the others all had combinations of cryptorchidism, micropenis, and hypospadias. Terminal 10q deletions appear to be strongly associated with abnormal male genital development, and should be specificcally searched for in the cytogenetic workup of such cases. © 1993 Wiley-Liss, Inc.