Difference between revisions of "Genital System - Abnormalities"

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Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Abnormalities ''Genital Abnormalities'']| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Disorders+of+Sex+Development ''Disorders of Sex Development'']
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Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Abnormalities ''Genital Abnormalities''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Disorders+of+Sex+Development ''Disorders of Sex Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Trisomy+X ''Trisomy X''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Turner+syndrome ''Turner syndrome''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Klinefelter+syndrome ''Klinefelter syndrome'']
  
 
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| {{ICD-11}} {{ICD11weblink}}423644907 Karyotype 47,XXX] - ''Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). Most individuals are only mildly affected or asymptomatic, the most common physical features including tall stature, epicanthal folds, hypotonia and clinodactyly, with seizures, renal and genitourinary abnormalities, and premature ovarian failure being also associated findings.''
 
| {{ICD-11}} {{ICD11weblink}}423644907 Karyotype 47,XXX] - ''Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). Most individuals are only mildly affected or asymptomatic, the most common physical features including tall stature, epicanthal folds, hypotonia and clinodactyly, with seizures, renal and genitourinary abnormalities, and premature ovarian failure being also associated findings.''
 
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{{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{{#pmid:20459843|PMID20459843}}.
 
{{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{{#pmid:20459843|PMID20459843}}.
  

Revision as of 15:03, 18 May 2019

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 ICD-11

Structural developmental anomalies of the male genital system - Micropenis or penis agenesis | Penile megalourethra | Diphallia | Penoscrotal transposition | Anorchia or microorchidia | Cryptorchidism | Hypospadias | Congenital chordee | Epispadias | Bifid scrotum | Agenesis of vas deferens | Absence or aplasia of prostate | Absence or aplasia of spermatic cord | Absence or aplasia of seminal vesicles | Polyorchidism | Meatal stenosis of penis | Hypoplasia of testis or scrotum | Genitoperineal median raphe cyst

Structural developmental anomalies of the female genital system - Structural developmental anomalies of vulva | Structural developmental anomalies of clitoris | Structural developmental anomalies of vagina | Structural developmental anomalies of cervix uteri | Structural developmental anomalies of uterus, except cervix | Structural developmental anomalies of ovaries, fallopian tubes or broad ligaments | Hydrocele of the canal of Nuck

See also - Structural developmental anomalies of the urinary system | Congenital adrenal hyperplasia | Structural developmental anomalies of the breast

Introduction

Cryptorchidism cartoon
Cryptorchidism

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).


Links: cryptorchidism | hypospadias

Genital Links: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | Female | X | ovary | corpus luteum | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Male | Y | SRY | testis | spermatozoa | ductus deferens | penis | prostate | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital
Historic Embryology - Genital 
1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1904 Leydig Cells | 1904 Hymen | 1905 Testis vascular | 1909 Prostate | 1912 Prostate | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1921 Urogenital Development | 1921 External Genital | 1927 Female Foetus 15 cm | 1932 Postnatal Ovary | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer

Some Recent Findings

  • Differences of sex development: the road to diagnosis[1] "The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. The aetiology of DSDs is very heterogenous and a precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies."
  • Ultrasonographic and multimodal imaging of pediatric genital female diseases[2] "Ultrasonography is the first-line imaging modality in the evaluation of the female pelvis in childhood and adolescence, because it is easy to perform, non-invasive and it does not require sedation. The transabdominal approach is preferred in children and adolescents, after filling the bladder to move away the bowel loops from the pelvis. The probe frequency must be adapted to age, thickness of tissues and depth of the structures under examination. High-frequency (4-12 MHz) linear or convex probes are used in newborns; high-frequency linear probes (4-12 MHz) in toddler, convex 5-7.5 MHz probes in girls and convex 3.5-5 MHz probes in teenagers. In this article, the main pathological conditions of the genital female tract in pediatric age are examined, such as congenital anomalies, disorders of sex development, ovarian cysts, ovarian tumors, adnexal torsion, primary amenorrhea, precocious puberty and pelvic inflammatory disease." ultrasound
  • Germany - Variations of sex development: The first German interdisciplinary consensus paper[3] "The term variations of sex development subsumes a large number of congenital conditions including chromosomal mosaics and variations of chromosomal, gonadal, and phenotypic sex. A situation of this nature may cause severe distress to both, parents and affected persons. One of the reasons for this is the binary form of gender classification in the society. In the past, because of a fear of possible stigmatization and an inability to cope with complex situations, it has been medical policy and practice for newborns to undergo early, mostly 'feminizing' elective surgery with the aim of achieving an outer genital appearance that is unambiguously male or female. Protests by advocacy groups for the most part as well as the results of outcome studies have shown that the development of affected persons may be very different to what has been expected and often does not result in the intended clear female or male gender identity as had been intended. CONCLUSION: The introduction of the consensus paper reflects on the emerging paradigm shift and the necessity for a more open view of gender within society. The paper is intended to aid the performance of appropriate diagnostics in DSD-affected newborns and especially to help parents and affected persons cope with the biological and social consequences of DSD. With regard to medical or surgical therapy, it gives information about the most recent treatment trends."
  • India - Clinical Spectrum of Disorders of Sex Development: A Cross-sectional Observational Study[4] "Disorders of sex development (DSD) constitutes a small but difficult and equally important area of endocrinology. SUBJECTS AND METHODS: This study was a cross-sectional observational study carried out in the department of pediatrics of a tertiary care hospital from August 2012 to August 2014. CONCLUSION: 46, XX DSD were the commonest etiological group in our study and CAH was the commonest individual disease. There is a need for educating general public and practitioners regarding DSD to allow early intervention. Moreover, there is a need to introduce routine neonatal screening for CAH in our country."
  • Japan - Nationwide Increase in cryptorchidism after the Fukushima Nuclear Accident[5] "To estimate the change of discharge rate after cryptorchidism surgery between pre- and post-disaster in Japan. The change in discharge rate between pre- and post-disaster was analysed using a Bayesian Generalized Linear Mixed Model (GLMM). Nationwide, a 13.4 % (95% credible interval 4.7-23.0 %) increase in discharge rates was estimated. The results of all sensitivity analyses were similar to the reported main results. The discharge rate of cryptorchidism was increased nationwide. The rates of low-weight babies or preterm births, risk factors of cryptorchidism, were almost constant during the study period, and age distribution of the surgery was also not changed, which suggested that the other factors that associated with the disaster increased the incidence of cryptorchidism." Japan Statistics cryptorchidism
More recent papers  
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

  • This search now requires a manual link as the original PubMed extension has been disabled.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

More? References | Discussion Page | Journal Searches | 2019 References

Search term: Genital Abnormalities | Disorders of Sex Development | Trisomy X | Turner syndrome | Klinefelter syndrome

Older papers  
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.

See also the Discussion Page for other references listed by year and References on this current page.

  • A collection of XY female cell lines[6] "Discordance between sexual phenotype and the 46,XY sex chromosome complement may be found in certain disorders of sexual development (DSD). Many of these DSD patients with female external genitalia and secondary sex characteristics have undescended testes and male internal genitalia. Causative mutations involving genes of the sex determining pathway, including the androgen receptor, SRY and the 5-alpha-reductase genes, are well-known, but the origin of other cases remain unresolved. In this report, we introduce our collection of lymphoblastoid lines derived from female patients with a 46,XY karyotype. These cell lines have been deposited and registered with the JCRB Cell Bank. They are available for comparison with other DSD cases and for further characterization of genetic loci involved in the mammalian sex determining pathway."
  • Nationwide Prevalence of Groin Hernia Repair[7] "Groin hernia repair is a commonly performed surgical procedure in the western world but large-scaled epidemiologic data are sparse. Large-scale data on the occurrence of groin hernia repair may provide further understanding to the pathophysiology of groin hernia development. This study was undertaken to investigate the age and gender dependent prevalence of groin hernia repair."
  • Anogenital Distance (AGD) and fertility.[8] "A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men."
  • The European Disorder of Sex Development Registry: A Virtual Research Environment.[9] "The EU-funded EuroDSD programme (www.eurodsd.eu) is one such collaboration involving clinical centres and clinical and genetic experts across Europe. At the heart of the EuroDSD collaboration is a European DSD registry and a targeted virtual research environment (VRE) that supports the sharing of DSD data."
  • Low testosterone levels in pre-term newborns born small for gestational age.{{#pmid:20503482|PMID20503482 "Previous studies showed that small for gestational age (SGA) newborns have an increased prevalence of hypospadias and other congenital defects of external genitalia. We observed that in the first days of life, SGA male pre-term newborns have reduced testosterone levels compared with adequate for gestational age pre-term newborns, independently from the presence of abnormalities of the external genitalia."

Human Genital Development Critical Periods

Human- genital development critical periods.jpg

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.[10] See also the Medical Journal of Australia 2009 editorial article.[11]
Disorders of Sexual Development - Terminology
New Terminology Previous Terminology
DSD Intersex
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


Contribution of AMH to DSD differential diagnosis[12]
DSD differential diagnosis with AMH
  • UDT - undescended testis
  • CAH - congenital adrenal hyperplasia
  • DSD - disorders of sex development
  • PMDS - persistent Müllerian duct syndrome
  • AMH - anti-Müllerian hormone
  • T - testosterone
  • AMHR - AMH receptor

International Classification of Diseases

 ICD-11

Structural developmental anomalies of the male genital system - Micropenis or penis agenesis | Penile megalourethra | Diphallia | Penoscrotal transposition | Anorchia or microorchidia | Cryptorchidism | Hypospadias | Congenital chordee | Epispadias | Bifid scrotum | Agenesis of vas deferens | Absence or aplasia of prostate | Absence or aplasia of spermatic cord | Absence or aplasia of seminal vesicles | Polyorchidism | Meatal stenosis of penis | Hypoplasia of testis or scrotum | Genitoperineal median raphe cyst

Structural developmental anomalies of the female genital system - Structural developmental anomalies of vulva | Structural developmental anomalies of clitoris | Structural developmental anomalies of vagina | Structural developmental anomalies of cervix uteri | Structural developmental anomalies of uterus, except cervix | Structural developmental anomalies of ovaries, fallopian tubes or broad ligaments | Hydrocele of the canal of Nuck

See also - Structural developmental anomalies of the urinary system | Congenital adrenal hyperplasia | Structural developmental anomalies of the breast

Sex Chromosome Abnormalities

Trisomy X

 ICD-11 Karyotype 47,XXX - Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). Most individuals are only mildly affected or asymptomatic, the most common physical features including tall stature, epicanthal folds, hypotonia and clinodactyly, with seizures, renal and genitourinary abnormalities, and premature ovarian failure being also associated findings.


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[13].

Trisomy X karyotype.jpg

Trisomy X karyotype


Links: Trisomy X

Turner Syndrome

 ICD-11 Turner syndrome - Karyotype missing one X chromosome (45, X0 or 45,XO/46,XX mosaicism) ; gonads: ovaries (streak); phenotype female with short stature, amenorrhea (hypergonadotrophic hypogonadism), absence of sexual development, webbed neck, low set ears, posterior hairline, widely-spaced nipples, short fourth metacarpals, and increased carrying angle at the elbow (cubitus valgus). Often associated with renal, cardiac and ocular abnormalities.

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 (45,X)

Turner syndrome karyotype (45,X)


Links: Monosomy X | Student Project - Turner syndrome

Klinefelter Syndrome

 ICD-11 Klinefelter syndrome - Klinefelter syndrome defines a group of chromosomal disorders in which there is at least one extra X chromosome compared with the normal 46,XY male karyotype. The effects on physical features and on physical and cognitive development increase with the number of extra X's, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15-16 points, with language most affected, particularly expressive language skills.

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.


Links: Klinefelter syndrome | Student Project - Klinefelter's syndrome

Congenital Adrenal Hyperplasia

 ICD-11 Congenital adrenal hyperplasia - Congenital adrenal hyperplasia (CAH) refers to a group of diseases associated with either complete (classical form) or partial (non-classical) anomalies in the biosynthesis of adrenal hormones. The disease is characterized by insufficient production of cortisol, or of aldosterone (classical form with salt wasting), associated with overproduction of adrenal androgens. In the classical form, metabolic decompensation (dehydration with hyponatremia, hyperkalemia and acidosis associated with mineralocorticoid deficiency, and hypoglycemia associated with glucocorticoid deficiency) may be life-threatening from the neonatal period onwards. Genital anomalies may be noted at birth in affected females.

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.[14]

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.[15]


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
Type Enzyme Deficiency Female Male
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

3-beta-hydroxysteroid dehydrogenase

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.
Links: Genital Abnormalities | Adrenal Development | Genes and Disease | OMIM 21 Deficiency | OMIM 17 Deficiency | OMIM 3 Deficiency

Prader Stages

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.


Prader Stages
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
Links:Genital - CAH | Adrenal - CAH | genital abnormalities)

Androgen Insensitivity Syndrome

There is a database (Androgen Receptor Gene Mutations) of 1,029 reported androgen receptor mutations.[16] 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.[17]

  • Partial androgen insensitivity syndrome - (PAIS) associated with impaired male genital development that can be transmitted through mutations in the androgen receptor.
Links: Androgen Receptor Gene Mutations Database

Cryptorchidism

 ICD-11 LB52 Cryptorchidism - A disorder affecting males, caused by an abnormality occurring in sex development during the antenatal period. This disorder is characterized by the absence of one or both testes from the scrotum. This disorder may also present with reduced fertility, psychological implications, or increased risk of testicular germ cell tumours. Confirmation is by imaging, karyotyping, or identification of male sex hormones in a blood sample.
Newborn - cryptorchidism normal birthweight[18]

The failure of testis descent is common abnormality in eutherian mammals.[19] 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.[20] 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.[21]
Cryptorchidism Types
True Ectopic
  • abdominal
  • inguinal
  • suprascrotal
  • prepenile
  • superficial ectopic
  • transverse scrotal
  • femoral
  • perineal
  Links: cryptorchidism | testis | genital abnormalities
Suprascrotal testis.jpg

Clinically exposed suprascrotal testis[21]

Testis descent is thought to have 2 phases:

  1. transabdominal descent - dependent on insulin-like hormone 3 (INSL3).
  2. inguinoscrotal descent - dependent on androgens.


Management of cryptorchidism in children: guidelines.[22] "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."


Links: testis | cryptorchidism

Undescended Ovaries

  • 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.

Hydrocele

 ICD-11

GB00 Hydrocele or spermatocele - A condition characterized by an accumulation of serous fluid in the tunica vaginalis testis or along the spermatic cord, and cystic swelling containing fluid and dead spermatozoa of the testicular epididymis, rete testis or efferent ductuli. Hydrocele of the canal of Nuck

  • 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

Human anogenital distance

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)

Human male anogenital distance graph.jpg A recent study in humans has shown that infertile men possessed significantly shorter mean AGD than fertile men.[8]


Compared to fathers, childless men had significantly shorter AGD (31.8 vs 44.6 mm, p<0.01).

Tract Abnormalities

Uterine anomalies ESHRE-ESGE classification
Uterine anomalies ESHRE-ESGE classification
Unicornate uterus

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 uterus01.jpg

Bicornuate uterus containing conceptus chorionic sac with placental cord on one side.

Uterine Duplication

(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.

Septate Uterus

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.[23]

  1. transverse testicular ectopia - one testis descends into the scrotum pulling the ipsilateral Fallopian tube into the inguinal canal (hernia uteri inguinalis).
  2. 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[24] 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: ovary abnormalities

Hypospadias

Classification of Hypospadias[25]

Hypospadias are the most common penis abnormality (1 in 300) and result from a failure of male urogenital folds to fuse in various regions.[26] 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.[25] 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.[27] Infants with hypospadias should not undergo circumcision.

Mouse models have shown that deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias.[28] 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.


Hypospadias Classification

Classification  ICD-11 Meatus Opening Image  Hypospadia classifications.jpg
Anterior glandular urinary meatus that opens at the site of the frenulum A
Coronal coronal urinary meatus opens in the ventral portion of the coronal sulcus B
Distal penile urinary meatus that opens along the shaft of the penis C
Penoscrotal penoscrotal urinary meatus opens where the shaft of the penis meets the scrotum D
Scrotal scrotal urinary meatus that opens on the scrotum E
Perineal perineal urinary meatus that opens in the perineum F
Table reference[25] Links: hypospadias | 'ICD-11 Hypospadias

Surgical Repair

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.


Links: Genital Abnormality - Hypospadia

Related Genetic Conditions

  • Johanson-Blizzard syndrome[29] - 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.

Splenogonadal Fusion

Rare abnormality resulting from fusion of the splenic and gonadal primordia during prenatal development.[30] 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.

Two classifications:

  • 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


Testicular Microlithiasis

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.


References

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  3. Krege S, Eckoldt F, Richter-Unruh A, Köhler B, Leuschner I, Menzel HJ, Moss A, Schweizer K, Stein R, Werner-Rosen K, Wieacker P, Wiesemann C, Wünsch L & Richter-Appelt H. (2018). Variations of sex development: The first German interdisciplinary consensus paper. J Pediatr Urol , , . PMID: 30713084 DOI.
  4. Dar SA, Nazir M, Lone R, Sameen D, Ahmad I, Wani WA & Charoo BA. (2018). Clinical Spectrum of Disorders of Sex Development: A Cross-sectional Observational Study. Indian J Endocrinol Metab , 22, 774-779. PMID: 30766817 DOI.
  5. Murase K, Murase J, Machidori K, Mizuno K, Hayashi Y & Kohri K. (2018). Nationwide Increase in Cryptorchidism after the Fukushima Nuclear Accident. Urology , , . PMID: 29751027 DOI.
  6. Kasai F & Ferguson-Smith MA. (2018). A collection of XY female cell lines. Hum. Cell , , . PMID: 29330774 DOI.
  7. Burcharth J, Pedersen M, Bisgaard T, Pedersen C & Rosenberg J. (2013). Nationwide prevalence of groin hernia repair. PLoS ONE , 8, e54367. PMID: 23342139 DOI.
  8. 8.0 8.1 Eisenberg ML, Hsieh MH, Walters RC, Krasnow R & Lipshultz LI. (2011). The relationship between anogenital distance, fatherhood, and fertility in adult men. PLoS ONE , 6, e18973. PMID: 21589916 DOI.
  9. Ahmed SF, Rodie M, Jiang J & Sinnott RO. (2010). The European disorder of sex development registry: a virtual research environment. Sex Dev , 4, 192-8. PMID: 20501980 DOI.
  10. Lee PA, Houk CP, Ahmed SF & Hughes IA. (2006). Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics , 118, e488-500. PMID: 16882788 DOI.
  11. Warne GL & Hewitt JK. (2009). Disorders of sex development: current understanding and continuing controversy. Med. J. Aust. , 190, 612-3. PMID: 19485836
  12. Xu HY, Zhang HX, Xiao Z, Qiao J & Li R. (2019). Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility. Asian J. Androl. , 21, 109-114. PMID: 30381580 DOI.
  13. Tartaglia NR, Howell S, Sutherland A, Wilson R & Wilson L. (2010). A review of trisomy X (47,XXX). Orphanet J Rare Dis , 5, 8. PMID: 20459843 DOI.
  14. Nimkarn S & New MI. (2009). Prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Mol. Cell. Endocrinol. , 300, 192-6. PMID: 19101608 DOI.
  15. Reisch N, Flade L, Scherr M, Rottenkolber M, Pedrosa Gil F, Bidlingmaier M, Wolff H, Schwarz HP, Quinkler M, Beuschlein F & Reincke M. (2009). High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. , 94, 1665-70. PMID: 19258407 DOI.
  16. Gottlieb B, Beitel LK, Nadarajah A, Paliouras M & Trifiro M. (2012). The androgen receptor gene mutations database: 2012 update. Hum. Mutat. , 33, 887-94. PMID: 22334387 DOI.
  17. Mooslehner KA, Davies JD & Hughes IA. (2012). A cell model for conditional profiling of androgen-receptor-interacting proteins. Int J Endocrinol , 2012, 381824. PMID: 22518120 DOI.
  18. Virtanen HE & Toppari J. (2008). Epidemiology and pathogenesis of cryptorchidism. Hum. Reprod. Update , 14, 49-58. PMID: 18032558 DOI.
  19. Amann RP & Veeramachaneni DN. (2007). Cryptorchidism in common eutherian mammals. Reproduction , 133, 541-61. PMID: 17379650 DOI.
  20. Moore CR. (1924). THE BEHAVIOR OF THE GERMINAL EPITHELIUM IN TESTIS GRAFTS AND IN EXPERIMENTAL CRYPTORCHID TESTES (RAT AND GUINEA PIG). Science , 59, 41-4. PMID: 17839834 DOI.
  21. 21.0 21.1 Favorito LA, Riberio Julio-Junior H & Sampaio FJ. (2017). Relationship between Undescended Testis Position and Prevalence of Testicular Appendices, Epididymal Anomalies, and Patency of Processus Vaginalis. Biomed Res Int , 2017, 5926370. PMID: 29445742 DOI.
  22. Gapany C, Frey P, Cachat F, Gudinchet F, Jichlinski P, Meyrat BJ, Ramseyer P, Theintz G & Burnand B. (2008). Management of cryptorchidism in children: guidelines. Swiss Med Wkly , 138, 492-8. PMID: 18726735 DOI.
  23. Rey R. (2005). Anti-Müllerian hormone in disorders of sex determination and differentiation. Arq Bras Endocrinol Metabol , 49, 26-36. PMID: 16544032 DOI.
  24. Norman RJ, Wu R & Stankiewicz MT. (2004). 4: Polycystic ovary syndrome. Med. J. Aust. , 180, 132-7. PMID: 14748678
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  28. Gredler ML, Seifert AW & Cohn MJ. (2015). Tissue-specific roles of Fgfr2 in development of the external genitalia. Development , 142, 2203-12. PMID: 26081573 DOI.
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Reviews

van der Horst HJ & de Wall LL. (2017). Hypospadias, all there is to know. Eur. J. Pediatr. , 176, 435-441. PMID: 28190103 DOI.

Acién P & Acién MI. (2011). The history of female genital tract malformation classifications and proposal of an updated system. Hum. Reprod. Update , 17, 693-705. PMID: 21727142 DOI.

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-

Articles

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


Books

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

Search Pubmed

Search Pubmed: Genital System Abnormalities | Disorders of Sex Development | Hypospadia

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Cite this page: Hill, M.A. (2019, September 15) Embryology Genital System - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_System_-_Abnormalities

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G