Microphallus Clinical Presentation

Updated: Nov 30, 2020
  • Author: Karen S Vogt, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Neonatal hypoglycemia is associated with other pituitary hormone deficiencies, including panhypopituitarism, growth hormone deficiency, and adrenal insufficiency. Other features that may be associated with hypopituitarism during the neonatal period include breech delivery, optic nerve hypoplasia, nystagmus, other midline defects, and cholestasis with prolonged direct hyperbilirubinemia.

Poor growth or failure to thrive is also associated with other pituitary hormone deficiencies.

An abnormal sense of smell (anosmia or hyposmia) suggests Kallmann syndrome (hypogonadotropic hypogonadism with abnormal olfaction).

Other congenital anomalies may provide clues to a genetic syndrome.

Family history of similarly affected children could suggest a familial form of hypogonadism or other hormone deficiency, defect in steroidogenesis (autosomal recessive), or androgen insensitivity (X-linked). Family history of unexplained death in the first year of life could suggest pituitary hormone deficiencies, adrenal insufficiency, or both.



The infant or child with micropenis should be thoroughly examined for dysmorphic features and other congenital anomalies.

This examination should include careful inspection of the face and mouth for cleft lip or palate or other indications of midfacial hypoplasia.

Abnormal growth velocity after the first 6-12 months of life suggests growth hormone deficiency with or without other pituitary hormone deficiencies.

A thorough examination of the genitalia, including proper measurements of the stretched penis length, position of the urethral opening, and location and size of the testes, is important. One or both testes may be abnormally descended because testosterone also plays a role in testicular descent.

The proper technique for measuring the penis is to use a rigid ruler held firmly against the symphysis pubis at a right angle. Firm but gentle traction is placed on the penis to stretch it upward along the ruler to the point of increased resistance. [1]

An alternate, less traumatic method is to use the index finger of one hand as a gauge pressed against the symphysis. As gentle traction is placed on the penis, the index finger of the other hand is used to mark the length on the gauge finger, and a tape measure is used to determine the length.



Micropenis most often results from fetal testosterone deficiency. Testosterone deficiency may be caused by a defect anywhere along the hypothalamic-pituitary-gonadal axis or a defect in peripheral androgen action (5-alpha reductase deficiency or PAIS). Micropenis may also be caused by isolated growth hormone deficiency. It can occur as a primary idiopathic structural anomaly or may be associated with a genetic syndrome. The most common cause of micropenis is abnormal hypothalamic or pituitary function that leads to hypogonadotropic hypogonadism. The next most common cause is a primary testicular disorder that leads to hypergonadotropic hypogonadism.

Conditions associated with hypogonadotropic hypogonadism

Kallmann syndrome

Anosmia (lack of sense of smell) or hyposmia is a prominent feature of Kallmann syndrome, which occurs in 1 per 10,000 males. The underlying abnormality is failure of migration of gonadotropin-releasing hormone (GnRH) and olfactory neurons from the olfactory placode to their proper locations in the hypothalamus and olfactory bulb, respectively. About half of males with Kallmann syndrome are born with a micropenis. The inheritance pattern is autosomal dominant (FGFR1/KAL-2 gene, among others), autosomal recessive, or X-linked recessive (KAL-1 gene). Associated anomalies may include cleft lip and palate, renal agenesis, sensorineural hearing loss, visual abnormalities, synkinesia (mirror image movements), cerebellar ataxia, agenesis of the corpus callosum, short metacarpals, or pes cavus. Abnormal or absent olfactory bulbs or sulci (folds) are seen on brain MRI in 90% of patients. [17, 18]

Isolated hypogonadotropic hypogonadism

Sense of smell is normal in this condition, differentiating it from Kallmann syndrome. [17]  An observational cohort study by Bonomi et al indicated that there is a greater tendency for a severe and complex phenotype to arise in Kallmann syndrome than in normosmic isolated hypogonadotropic hypogonadism. [19]

Multiple pituitary hormone deficiencies

Hypoglycemia may occur due to growth hormone and adrenocorticotrophic hormone (ACTH) deficiencies. Midline defects and cholestatic liver disease can be associated. Hypopituitarism may be secondary to transcription factor mutations (eg, PROP-1, LHX3); however, in most instances, genetic evaluation is not part of the routine diagnostic evaluation. [20, 21]

Septo-optic dysplasia (SOD)

Major features of SOD include the triad of absent septum pellucidum, optic nerve hypoplasia, and hypopituitarism. Wandering nystagmus may be present. The multiple pituitary hormone deficiencies may be present at birth or develop over years. Mutations in the HESX1 gene (RPX) have been associated with SOD. [20, 21]

Conditions associated with decreased testosterone production and hypergonadotropic hypogonadism


In this condition, also known as vanishing testes or testicular regression syndrome, testes are absent in an individual with a normal male karyotype. Micropenis results when testicular degeneration occurs after 12-14 weeks' gestation. The testicular degeneration is likely due to torsion or other vaso-occlusive event in utero. [10, 11]

LH-receptor defects

Autosomal recessive mutations are found in the LHCGR gene in this rare condition and cause Leydig cell hypoplasia in males. The genital phenotype varies from normal-appearing female to male with micropenis. [16, 22]

Defects in testosterone steroidogenesis

Incomplete forms of 17 beta-hydroxysteroid dehydrogenase deficiency type 3 can cause micropenis, but the genitalia are most often female in appearance or less often ambiguous. The enzyme 17-beta-hydroxysteroid dehydrogenase normally converts androstenedione to testosterone. In the deficiency state, the androstenedione-to-testosterone ratio is elevated (after hCG stimulation in the prepubertal state) and is expressed as a testosterone-to-androstenedione ratio of less than 0.8. These individuals undergo profound virilization at puberty. [10, 23, 24]

Deficiency of 5-alpha reductase

5-alpha reductase peripherally converts testosterone to the more potent DHT, which is necessary for virilization of the male external genitalia. The genitalia in most children with this autosomal recessive condition are usually more ambiguous, with varying degrees of incomplete labioscrotal fusion and hypospadias. The hallmark biochemical abnormality is an elevated testosterone-to-DHT ratio (usually >30:1) after hCG stimulation if prepubertal. These individuals also undergo profound virilization at puberty. Genetic testing for SRD5A2 gene mutations is commercially available. [15, 25, 26]

Partial androgen insensitivity syndrome

PAIS is caused by a defect in the androgen receptor. Isolated micropenis is not typically a manifestation of PAIS because the genitalia are usually more ambiguous. Gonadotropin and testosterone levels are elevated in this condition. Because the gene that codes for the androgen receptor is located on the X chromosome, PAIS is inherited in an X-linked manner. [11]

Genetic syndromes

Klinefelter syndrome (47,XXY) and other poly X syndromes

Features of this syndrome include hypergonadotropic hypogonadism, tall stature, gynecomastia, small firm testes, increased leg length in proportion to height, and increased risk for learning difficulties. [27]

Prader-Willi syndrome (PWS)

Hypogonadism is a feature of PWS and usually manifests in males as cryptorchidism and an underdeveloped scrotum. Some also have a micropenis. Characteristic features of PWS include hypotonia, weak suck, feeding difficulties and failure to thrive in infancy with later development of hypothalamic hyperphagia and often obesity. Motor and language developmental delay, short stature, small hands and feet, emotional instability (perseveration, obsessions and compulsions), almond-shaped eyes, and triangular mouth are additional features. PWS occurs in 1:20,000 live births. The underlying genetic abnormality is the lack of expression of genes on the Prader-Willi critical region, 15q11.2-13, of the paternally inherited chromosome 15, which may be due to deletion (70%), maternal uniparental disomy (25%), or a imprinting defect (5%). [28]

Bardet-Biedl syndrome

Features of this syndrome include hypogonadotropic hypogonadism, rod-cone dystrophy with progressive visual impairment, obesity, short stature, polydactyly, developmental delay, renal anomalies leading to end-stage renal disease, and hepatic fibrosis. Inheritance of this syndrome is in an autosomal recessive pattern and mutations in 14 genes have been implicated. [29]

Noonan syndrome

Features of this syndrome include short stature, webbed neck, hypertelorism, ptosis, low posterior hairline, low-set ears, pectus excavatum, cryptorchidism, valvular pulmonary stenosis, lymphedema, and bleeding abnormalities. Noonan syndrome is inherited in an autosomal dominant manner, although approximately half of all cases represent new mutations. Mutations in the PTPN11 gene are found in 50% and smaller percentages have mutations in KRAS, SOS1, and RAF1. [30]

CHARGE syndrome

The syndrome is defined by coloboma, heart disease, atresia choanae, retarded growth and development, genital anomalies and hypogonadism, and ear anomalies and deafness. Neuropathic bladder, hydronephrosis, vesicoureteral reflux, and ureteropelvic junction obstruction may also occur. Given these potential renal and urinary tract abnormalities, bladder and renal ultrasonography and voiding cystourethrography (VCUG) are indicated in those suspected of having this syndrome. Sixty to seventy percent have a mutation in the CHD7 gene. [31, 32]


More rare genetic syndromes associated with micropenis include Robinow syndrome, Rud syndrome, and IMAGe syndrome. [14]