Genital System - Abnormalities
|Embryology - 20 Mar 2019 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Human Genital Development Critical Periods
- 4 International Classification of Diseases
- 5 Disorders of Sex Development
- 6 Sex Chromosome Abnormalities
- 7 Congenital Adrenal Hyperplasia
- 8 Prader Stages
- 9 Androgen Insensitivity Syndrome
- 10 Cryptorchidism
- 11 Undescended Ovaries
- 12 Hydrocele
- 13 Tract Abnormalities
- 14 Polycystic Ovary Syndrome
- 15 Hypospadias
- 16 Splenogonadal Fusion
- 17 Testicular Microlithiasis
- 18 References
- 19 External Links
- 20 Glossary Links
How and why do things go wrong in development?
Human genital abnormalities are currently described as "Disorders of Sex Development" (DSD) and includes: chromosomal, gonadal dysfunction, tract abnormalities, external genitalia and gonadal descent. The genital system is closely associated developmentally and anatomically with the renal system, often called the "urogenital system", therefore abnormalities of renal development should also be considered when studying this topic.
- The earlier term "intersex" and a variety of other previously applied terms related to genetic abnormalities have been replaced by the term "Disorders of sex development" (DSD).
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
|These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
Human Genital Development Critical Periods
International Classification of Diseases
The International Classification of Diseases (ICD) World Health Organization's classification used worldwide as the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems. Version ICD-11 coding is currently being introduced to replace ICD-10.
|Female genital organs
||Male genital organs
|Within the ICD10 classification "congenital malformations, deformations and chromosomal abnormalities" are (Q00-Q99) but excludes "inborn errors of metabolism" (E70-E90).
ICD-10 Congenital malformations of genital organs (Q50-Q56) Excl.: androgen resistance syndrome (E34.5) syndromes associated with anomalies in the number and form of chromosomes (90-99) testicular feminization syndrome (E34.5)
ICD-10 Congenital malformations of ovaries, fallopian tubes and broad ligaments (Q50)
ICD-10 Congenital malformations of uterus and cervix (Q51)
ICD-10 Other congenital malformations of female genitalia (Q52)
ICD-10 Undescended testicle (Q53)
ICD-10 Hypospadias Template:Q54 Excl.: epispadias (64.0)
ICD-10 Other congenital malformations of male genital organs (Q55)
Excl.: congenital hydrocele (P83.5) hypospadias (54.-)
Excl.: pseudohermaphroditism: female, with adrenocortical disorder (E25.-) male, with androgen resistance (E34.5) with specified chromosomal anomaly (96-99)
Please note that this category uses old terminology, that has been replaced elsewhere with "Disorders of Sex Development (DSD)".
Disorders of Sex Development
The previous human sex development terminology (true hermaphrodites, male pseudohermaphrodites and female pseudohermaphrodites) are considered outdated and stigmatising and have been replaced with the general term Disorders of Sex Development (DSD) established by the Consensus statement on management of intersex disorders. See also the Medical Journal of Australia 2009 editorial article.
|New Terminology||Previous Terminology|
|46,XY DSD||Male pseudohermaphrodite|
undervirilization of an XY male
undermasculinization of an XY male
|46,XX DSD||Female pseudohermaphrodite|
overvirilization of an XX female
masculinization of an XX female
|Ovotesticular DSD||True hermaphrodite|
|46,XX testicular DSD||XX male or XX sex reversal|
|46,XY complete gonadal dysgenesis||XY sex reversal|
Sex Chromosome Abnormalities
Trisomy X is a caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). This is also the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births with some individuals are only mildly affected or asymptomatic. It is estimated that only 10% of individuals with trisomy X are actually diagnosed. Common physical features include: tall stature, epicanthal folds, hypotonia and clinodactyly. Other physical features include: neural (seizures), renal and genitourinary abnormalities, and premature ovarian failure (POF) (see review.
Trisomy X karyotype
- Links: Trisomy X
Turner syndrome or Monosomy X (45,X) feature include gonadal dysgenesis and short stature. Named after Henry Turner, an American clinician who first described (1938) the syndrome.
Turner syndrome karyotype (45,X)
Klinefelter syndrome (47,XXY) caused by an additional X chromosome (or more) in affected males> Named after Harry F. Klinefelter who first described (1942) the syndrome. Common physical features include reduced fertility and hypogonadism. Some individuals are only mildly affected or asymptomatic and the severity varies greatly between individuals.
Congenital Adrenal Hyperplasia
The adrenal abnormality of congenital adrenal hyperplasia (CAH) is an impairment of cortisol production by the adrenal cortex, is one of the most common causes of DSD genitalia at birth
- genetically male (XY) infants born with undervirilized genitalia (androgen insensitivity syndrome, cloacal exstrophy) are generally assigned and reared as girls.
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be prenatally diagnosed in utero through molecular genetic analysis of fetal DNA. Prenatal treatment by dexamethasone administration to the at-risk pregnant mother has been shown to be effective in reducing genital virilization in the fetus, avoiding unnecessary postnatal genitoplasty in affected females.
There has been recorded a prevalence of reduced fecundity in men with congenital adrenal hyperplasia, related to testicular adrenal rest tumours and poor semen parameters.
Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A, is the most common form of CAH, accounting for more than 90% of cases
Deficiency of 17-hydroxylase is the less common form of CAH.
|Congenital Adrenal Hyperplasia|
|classic virilizing adrenal hyperplasia||21-hydroxylase, 11-beta-hydroxylase,
or 3-beta-hydroxysteroid dehydrogenase
|ambiguous genitalia at birth - complete or partial fusion of the labioscrotal folds and a phallic urethra to clitoral enlargement (clitoromegaly), partial fusion of the labioscrotal folds, or both||normal genitalia, present at age 1-4 weeks with salt wasting (classic salt-wasting adrenal hyperplasia)|
|simple virilizing adrenal hyperplasia||mild 21-hydroxylase||identified later in childhood because of precocious pubic hair, clitoral enlargement (clitoromegaly), or both, often accompanied by accelerated growth and skeletal maturation||early genital development (pubic hair and/or phallic enlargement) accelerated growth and skeletal maturation|
|nonclassic adrenal hyperplasia||milder deficiencies of 21-hydroxylase
or 3-beta-hydroxysteroid dehydrogenase
|present at puberty or adult with infrequent menstruation (oligomenorrhea), abnormal hair growth (hirsutism), and/or infertility|
|17-hydroxylase deficiency syndrome||17-hydroxylase deficiency or
|rare, phenotypically female at birth do not develop breasts or menstruate in adolescence and may have hypertension||steroidogenic acute regulatory (StAR) deficiency have ambiguous genitalia or female genitalia, at puberty may lack breast development and may have hypertension|
|This is a complex steroidogenic abnormality, and the above table of clinical descriptions are provided only a guide.|
Also called the Prader scale, a clinical classification system used to describe virilization of female genitalia, mainly associated with the congenital adrenal hyperplasia (CAH). Two normal (Stage 0 – Normal female genitalia; Stage 6 – Normal male genitalia) and five distinct abnormal stages ( 1 to 5 increasing virilisation). Named after Dr. Andrea Prader (1919 – 2001) an endocrinologist who also discovered the Prader-Willi syndrome and developed a second male testis development scale the Orchidometer.
|Stage 0||Normal female genitalia.|
|Stage 1||Mildly enlarged clitoris, slightly reduced vaginal opening, usually within normal variations.|
|Stage 2||Abnormal genitalia clearly seen by eye, phallus being intermediate in size, small vaginal opening with separate urethral opening. Posterior labial fusion present.|
|Stage 3||Further enlarged phallus than Stage 2, with single urogenital sinus and nearly complete fusion of the labia.|
|Stage 4||Upon examination, looks more male than female, with an empty scrotum and a normal-sized penis-like phallus, however this structure is not quite as free from the perineum to be pulled onto the abdomen towards the umbilicus. A small urethral/vaginal opening at the base of the shaft/phallus (hypospadias in a male), with an x-ray showing the internal connection with the upper vagina and uterus.|
|Stage 5||Complete male virilisation, a normally-formed penis is present. Urethral opening at or near the tip, and the scrotum formed, but empty. Internal organs in the pelvis include normal ovaries and uterus, with the vagina connecting internally with the urethra (as in Stage 4). Newborn infants are not seen to be visibly ambiguous, and are assumed to be normal boys (with undescended testes). The diagnosis of CAH is not apparent until signs of salt-wasting develop, about a week later.|
|Stage 6||Normal male presentation of the penis with normal testes.|
|Links: Genital - CAH | Adrenal - CAH | Female | Genital System - Abnormalities | Genital Terms|
Androgen Insensitivity Syndrome
There is a database (Androgen Receptor Gene Mutations) of 1,029 reported androgen receptor mutations. Complete androgen insensitivity syndrome affects 2 to 5 per 100,000 people.
A recent article has also looked in cell culture at the androgen receptor interacting proteins.
- Partial androgen insensitivity syndrome - (PAIS) associated with impaired male genital development that can be transmitted through mutations in the androgen receptor.
The failure of testis descent is common abnormality in eutherian mammals. The external location of the testes in the scrotum acts as a local thermo-regulator and provides a temperature environment below that of the general body temperature. This thermal function is essential for normal spermatogenesis and cryptorchidism therefore affects fertility.
- Abnormality of either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males.
- Descent may complete postnatally in the first year, failure to descend can result in sterility.
- Undescended testis has a higher risk of the anatomical anomalies testicular appendices, epididymal anomalies, and processus vaginalis.
Clinically exposed suprascrotal testis
Testis descent is thought to have 2 phases:
- transabdominal descent - dependent on insulin-like hormone 3 (INSL3).
- inguinoscrotal descent - dependent on androgens.
Management of cryptorchidism in children: guidelines. "Cryptorchidism is best diagnosed clinically, and treated by surgical orchiopexy at age 6-12 months, without a routine biopsy. If no testis is palpable, or if other signs of hypovirilisation such as hypospadias are present, the chromosomal sex and hormonal status must be assessed. Laparoscopy is the best way of diagnosing and managing intra-abdominal testes."
- reasonably rare gonad abnormality, often detected following clinical assessment of fertility problems and may also be associated with other uterine malformations (unicornuate uterus).
- Due to the relative positions of the male (external) and female (internal) gonads and the pathways for their movement, failure of gonad descent is more apparent and common in male cryptorchidism than female undescended ovaries.
- Male Hydrocele is a fluid-filled cavity of either testis or spermatic cord, where peritoneal fluid passes into a patent processus vaginalis.
- Female Hydrocele is a similar, but rarer, fluid-filled cavity occuring in the female as a pouch of peritoneum extending into the labium majorum (canal of Nuck).
Anogenital Distance (AGD) is a clinical measurement of a parameter that is sexually dimorphic for genital development. This distance, from the posterior aspect of the scrotum to the anal verge, has been used as a marker for endocrine disruption in animal studies and may also be shorter in infant males with genital anomalies (More? see related references)
|A recent study in humans has shown that infertile men possessed significantly shorter mean AGD than fertile men.
Many different forms
- Uterine: associated with other anomolies, unicornuate uterus
- Vagina: agenesis, atresia
- Ductus Deferens: Unilateral or bilateral absence, failure of mesonephric duct to differentiate
Bicornuate uterus containing conceptus chorionic sac with placental cord on one side.
(uterus didelphys, double uterus, uterus didelphis) A rare uterine developmental abnormality where the paramesonephric ducts (Mullerian ducts) completely fail to fuse generating two separate uterus parts each connected to the cervix and having an ovary each.
Cervical: cervical agenesis, cervical duplication
Vaginal: Mayer-Rokitansky syndrome (MRK anomaly, Rokitansky-Küster-Hauser syndrome, RKH syndrome, RKH) congenital absence of the vagina, dyspareunia, vaginal agenesis.
Male - Persistent Müllerian Duct Syndrome
Persistent Müllerian Duct Syndrome (PMDS) men are genotypic and externally phenotypic males with cryptorchidism, sometimes associated with inguinal hernia.
- transverse testicular ectopia - one testis descends into the scrotum pulling the ipsilateral Fallopian tube into the inguinal canal (hernia uteri inguinalis).
- bilateral cryptorchidism - the uterus is fixed in the pelvis and both testes are embedded in the broad ligament in ovarian position.
Polycystic Ovary Syndrome
(PCOS) or Stein–Leventhal syndrome (1930s researchers) a metabolic syndrome with many other symptoms, ovarian cysts arise through incomplete follicular development or failure of ovulation. For review see It has recently been suggested (NIH workshop 2012) that the name "Polycystic Ovary Syndrome" is not appropriate for the condition and should be renamed.
- Links: Template:Ovary abnormalities
Hypospadias are the most common penis abnormality (1 in 300) and result from a failure of male urogenital folds to fuse in various regions. This in turn leads to resulting in a proximally displaced urethral meatus. The cause is unknown, but suggested to involve many factors either individually or in combination including: familial inheritance, low birth weight, assisted reproductive technology, advanced maternal age, paternal subfertility and endocrine-disrupting chemicals. Maternal hypertension during pregnancy has also been shown to double the risk and a pregnancy diet lacking meat and fish also show an increase in hypospadias. Infants with hypospadias should not undergo circumcision.
Mouse models have shown that deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias. Fgfr2 was expressed in two epithelial populations, the endoderm-derived urethral epithelium and the ectoderm-derived surface epithelium and urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the lower urethra were controlled by discrete regions of Fgfr2 activity.
|Anterior||Q54.1||on inferior surface of glans penis||A|
|Coronal||Q54.0||in balanopenile furrow||B|
|Distal||Q54.0||on distal third of shaft||C|
|Penoscrotal||Q54.2||at base of shaft in front of scrotum||D|
|Scrotal||on scrotum or between the genital swellings||E|
|Perineal||Q54.3||behind scrotum or genital swellings||F|
|Table reference Links: hypospadias|
Depending on the class of hypospadias there are a number of different surgical repair techniques including: orthoplasty or penile straightening, urethroplasty, meatoplasty and glanuloplasty, scrotoplasty (oscheoplasty) and skin coverage.
Related Genetic Conditions
- Johanson-Blizzard syndrome - hypospadias, failure to thrive, exocrine pancreatic deficiency, short stature and developmental delay, cutis aplasia on the scalp, aplasia of alae nasi, hypothyroidism, myxomatous mitral valve, and patent ductus arteriosus.
Rare abnormality resulting from fusion of the splenic and gonadal primordia during prenatal development. On the left side and more common in male and adhesion to the gonad, epididymis or ductus deferens and then follows the caudal descent with the gonad. Failure of complete descent can also result in associated intraabdominal cryptorchism.
- continuous - orthotopic spleen connects to the gonad with a cord of fibrous or splenic tissue.
- discontinuous - no connection between the orthotopic spleen and gonad.
- Links: Spleen Development
Adult male testis abnormality associated with the deposition of multiple tiny calcifications throughout the testes (usually bilateral), detected by ultrasound. Present in up to 5.6% of the general adult population between 17 and 35 years of age. Also present in about 50% of men with a germ cell tumour.
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Ostrer, H. 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis GeneReviews Pagon RA, Bird TD, Dolan CR, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-
Austin J, Tamar-Mattis A, Mazur T, Henwood MJ & Rossi WC. (2011). Disorders of sex development-when and how to tell the patient. Pediatr Endocrinol Rev , 8, 213-7; quiz 223. PMID: 21525798
Evaluation and Treatment of Cryptorchidism. Penson DF, Krishnaswami S, Jules A, Seroogy JC, McPheeters ML. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Dec. PMID 23326894
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- DSD Consortium Guidelines | Handbook for Parents
- EuroDSD EuroDSD programme is a collaboration of doctors and scientists from all over Europe. Long-term outcome studies on the various DSD entities are desperately needed in order to establish a basis for evidence-based medicine regarding sex assignment and conservative and surgical treatment options.
- German DSD network
- Italian registry for DSD
- Intersex Society of North America
- Turner Syndrome Society of the U.S.
- Androgen Receptor Gene Mutations Database
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Cite this page: Hill, M.A. (2019, March 20) Embryology Genital System - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_System_-_Abnormalities
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