Microphallus 

Microphallus, or micropenis, is defined as a stretched penile length of less than 2.5 standard deviations (SDs) below the mean for age. Traditionally, the term micropenis refers to a penis that is otherwise normally formed, and the term microphallus has been used when associated hypospadia is present.

The mean stretched penile length in a full-term newborn male is 3.5 cm. Measurements of less than 2-2.5 cm (2.5 SDs below the mean) in a full-term newborn male meet the definition of micropenis and warrant evaluation.^{[1, 2, 3, 4]} Penile growth is essentially linear during mid-to-late gestation. Tuladhar et al (1998) reported the following formula to describe the relationship between penile length and gestational age for infants born at 24-36 weeks gestation:^[5]

Penile length in centimeters = -2.27 + 0.16 X (gestational age in weeks)

Although micropenis can be considered a form of ambiguous genitalia, the presence of a normal scrotum and palpable testes indicates a high probability of a normal male karyotype. If the testes are not palpable and/or the penile urethra is absent, the examination is better described as ambiguous, and an evaluation and counseling for disorders of sex development should be performed.

After the first few years of life, the penis grows very little until puberty when testosterone levels begin to rise. Mean stretched penile lengths and 2.5 SDs below the mean for various age groups can be found in the popular Harriet Lane Handbook (Table 10-15, 19th ed.).^[6]

Occasionally, older boys are brought for evaluation because of concerns of small genitalia. These boys are usually prepubertal and obese. Most often, these individuals have normal penis size based on stretched penile length, and the apparent smallness is secondary to the penis being concealed in the suprapubic fat pad. However, if the penis does measure less than 2.5 SDs below the mean (approximately 4 cm), further evaluation is indicated.

Fetal production of testosterone and its peripheral conversion to dihydrotestosterone (DHT) is necessary for normal male development. Early in gestation, placental human chorionic gonadotropin (hCG) stimulates the developing testes to produce testosterone through binding to the luteinizing hormone (LH) receptor. By approximately 14 weeks' gestation, the fetal hypothalamic-pituitary-gonadal axis is active, and testosterone production falls under the control of fetal LH. Therefore, penile growth after the first trimester depends on fetal testosterone production. Testosterone is peripherally converted by the enzyme 5-alpha reductase to the more potent androgen DHT, which is responsible for virilization of the male external genitalia. Finally, intact peripheral androgen receptors are necessary for normal male development.^[7]

After an initial surge of LH and testosterone at birth, lasting about 12 hours, gonadotropin (LH and follicle stimulating hormone [FSH]) and testosterone levels are low during the first few days of life. At about age 1 week, gonadotropin and testosterone levels begin to rise to pubertal levels, peaking at age 1-3 months, and then decreasing to prepubertal levels by age 6 months.^{[8, 9]} After age 6 months, the little subsequent penile growth that occurs parallels general somatic growth. With the onset of puberty penis growth resumes because of increased testosterone production. Growth hormone also plays a role in penis growth as micropenis has been observed in children with isolated growth hormone deficiency.

Micropenis may be caused by a defect anywhere along the hypothalamic-pituitary-gonadal axis, a defect in peripheral androgen action, isolated growth hormone deficiency, a primary structural anomaly, or may be part of a genetic syndrome. The most common cause of micropenis is abnormal hypothalamic or pituitary function. In the absence of normal hypothalamic or pituitary function, a normally shaped penis may develop due to maternal hCG effect on fetal testosterone production, but adequate penile growth does not occur after 14 weeks' gestation when testosterone production depends on intact fetal pituitary LH secretion. Failure of adequate testosterone production toward the end of gestation due to a primary testicular disorder can also result in inadequate penis growth.

Micropenis can also occur in children with LH-receptor defects and defects in testosterone biosynthesis (e.g. 17-beta hydroxysteroid dehydrogenase deficiency).^[8] The genitalia of individuals with LH-receptor defects vary from normal female-appearing to male-appearing with micropenis. Individuals with 17-beta hydroxysteroid dehydrogenase deficiency most often have female-appearing genitalia and, less often, ambiguous genitalia.^[10]

Defects in peripheral androgen action include 5-alpha reductase deficiency (failure of conversion of testosterone to DHT) and partial androgen insensitivity syndrome (PAIS) due to an androgen receptor defect. However, most children with these conditions have varying degrees of incomplete labioscrotal fusion, resulting in hypospadias and genital ambiguity.^[10]

Lastly, genetic syndromes in which micropenis may be a feature include Prader-Willi, Klinefelter, and Noonan syndromes, among others (see Causes).^[10]

Mortality/Morbidity

When micropenis is associated with hypopituitarism and hypoadrenalism, the infant can develop hypoglycemia, electrolyte abnormalities, hypotension, and shock. Infants with midline defects and those with optic nerve hypoplasia or aplasia deserve particular attention because these defects can be associated with pituitary hormone deficiencies. Failure to recognize this association in an ill neonate can result in death. Infants who survive the newborn period may exhibit varying degrees of poor growth and failure to thrive, depending on potential associated hormone deficiencies or genetic syndrome.

Psychosocial concerns can arise over issues such as gender identity, normal standing urination, physical appearance, and sexual performance. These concerns should be addressed with early evaluation, treatment and counseling, if appropriate.

In cases of extreme micropenis, especially if associated with other genital anomalies (e.g., cryptorchidism, hypospadias), gender reassignment is sometimes considered. However, the family should be intimately involved in this decision, and counseling from a center with a multidisciplinary team skilled at gender reassignment should be pursued.

Sex

By definition, microphallus is an exclusively male condition. However, distinguishing between a male with micropenis and bilateral cryptorchidism and a female with clitoromegaly is important and may be difficult.

Age

Micropenis is most often recognized and evaluated in the immediate newborn period, but delays in evaluation may also occur.