Genital System - Abnormalities

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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The earlier term "intersex" and a variety of other previously applied terms related to genetic abnormalities have been replaced by the term "disorders of sex development" (DSD).


Genital Links: Introduction | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Reproductive Cycles | Menstrual Cycle | Male | Testis | Spermatozoa | Penis | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
Historic Embryology - Genital 
1902 The Uro-Genital System | 1904 Ovary and Testis | 1904 Leydig Cells | 1904 Hymen | 1905 Testis vascular | 1912 Urinogenital Organ Development | 1914 Female | 1915 Cowper’s and Bartholin’s Glands | 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

  • Nationwide Prevalence of Groin Hernia Repair [1] "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.[2] "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.[3] "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.[4] "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."
More recent papers
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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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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.

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Search term: Genital Abnormalities

Ying Hsu, Janelle E Garrison, Gunhee Kim, Addison R Schmitz, Charles C Searby, Qihong Zhang, Poppy Datta, Darryl Y Nishimura, Seongjin Seo, Val C Sheffield BBSome function is required for both the morphogenesis and maintenance of the photoreceptor outer segment. PLoS Genet.: 2017, 13(10);e1007057 PubMed 29049287

Sudip Kumar Ghosh, Abhijit Dutta, Sharmila Sarkar, Shanka Subhra Nag, Surajit Kumar Biswas, Prabhakar Mandal Focal Dermal Hypoplasia (Goltz Syndrome): A Cross-sectional Study from Eastern India. Indian J Dermatol: 2017, 62(5);498-504 PubMed 28979012

Anne Elodie Millischer, David Grevent, Véronique Rousseau, Neil O'Gorman, Pascale Sonigo, Bettina Bessieres, Yves Ville, Nathalie Boddaert, Laurent J Salomon Fetal MRI compared to Ultrasound for the diagnosis of obstructive genital malformations. Prenat. Diagn.: 2017; PubMed 28921932

Linn Håkonsen Arendt, Morten Søndergaard Lindhard, Tine Brink Henriksen, Axel Forman, Jørn Olsen, Cecilia Høst Ramlau-Hansen Maternal endometriosis and genital malformations in boys: a Danish register-based study. Fertil. Steril.: 2017; PubMed 28863937

Fortunato Lonardo, Maria Serena Lonardo, Fabio Acquaviva, Matteo Della Monica, Francesca Scarano, Gioacchino Scarano Say-Barber-Biesecker-Young-Simpson syndrome and Genitopatellar syndrome: lumping or splitting? Clin. Genet.: 2017; PubMed 28857140


Search term: Disorders of Sex Development Vicki N Meyers-Wallen, Adam R Boyko, Charles G Danko, Jennifer K Grenier, Jason G Mezey, Jessica J Hayward, Laura M Shannon, Chuan Gao, Afrah Shafquat, Edward J Rice, Shashikant Pujar, Stefanie Eggers, Thomas Ohnesorg, Andrew H Sinclair XX Disorder of Sex Development is associated with an insertion on chromosome 9 and downregulation of RSPO1 in dogs (Canis lupus familiaris). PLoS ONE: 2017, 12(10);e0186331 PubMed 29053721

K L Garand, Ryan Schwertner, Amy Chen, William G Pearson Computational Analysis of Pharyngeal Swallowing Mechanics in Patients with Motor Neuron Disease: A Pilot Investigation. Dysphagia: 2017; PubMed 29052789

L Ramos, B Chávez, L Mares, E Valdés, F Vilchis Mutational analysis of the androgen receptor (NR3C4) gene in patients with 46,XY DSD. Gene: 2017; PubMed 29051026

María Mar López-Rodríguez, José Granero Molina, Isabel María Fernández Medina, Cayetano Fernández Sola, Alicia Ruiz Muelle Patterns of food avoidance and eating behavior in women with fibromyalgia. [Patrones de evitación y conductas alimentarias en pacientes con fibromialgia.] Endocrinol Diabetes Nutr: 2017, 64(9);480-490 PubMed 29050704

Michelle A Clementi, Grace S Kao, Evelyn Monico Pain Acceptance as a Predictor of Medical Utilization and School Absenteeism in Adolescents With Chronic Pain. J Pediatr Psychol: 2017; PubMed 29048520

Human Genital Development Critical Periods

Human- genital development critical periods.jpg


International Classification of Diseases

ICD 10 - XVII Congenital Malformations

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. Within this classification "congenital malformations, deformations and chromosomal abnormalities" are (Q00-Q99) but excludes "inborn errors of metabolism" (E70-E90).

ICD10 Congenital malformations of genital organs (Q50-Q56) 
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. Includes this section on XVII Congenital Malformations.
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)

Q50 Congenital malformations of ovaries, fallopian tubes and broad ligaments
  • Q50.0 Congenital absence of ovary Excl.: Turner's syndrome (96.-)
  • Q50.1 Developmental ovarian cyst
  • Q50.2 Congenital torsion of ovary
  • Q50.3 Other congenital malformations of ovary Accessory ovary Congenital malformation of ovary NOS Ovarian streak
  • Q50.4 Embryonic cyst of fallopian tube Fimbrial cyst
  • Q50.5 Embryonic cyst of broad ligament Cyst: epoophoron Gartner's duct parovarian
  • Q50.6 Other congenital malformations of fallopian tube and broad ligament Absence Accessory Atresia (of) fallopian tube or broad ligament Congenital malformation of fallopian tube or broad ligament NOS
Q51 Congenital malformations of uterus and cervix
  • Q51.0 Agenesis and aplasia of uterus Congenital absence of uterus
  • Q51.1 Doubling of uterus with doubling of cervix and vagina
  • Q51.2 Other doubling of uterus Doubling of uterus NOS
  • Q51.3 Bicornate uterus
  • Q51.4 Unicornate uterus
  • Q51.5 Agenesis and aplasia of cervix Congenital absence of cervix
  • Q51.6 Embryonic cyst of cervix
  • Q51.7 Congenital fistulae between uterus and digestive and urinary tracts
  • Q51.8 Other congenital malformations of uterus and cervix Hypoplasia of uterus and cervix
  • Q51.9 Congenital malformation of uterus and cervix, unspecified
Q52 Other congenital malformations of female genitalia
  • Q52.0 Congenital absence of vagina
  • Q52.1 Doubling of vagina Septate vagina Excl.: doubling of vagina with doubling of uterus and cervix (51.1)
  • Q52.2 Congenital rectovaginal fistula Excl.: cloaca (43.7)
  • Q52.3 Imperforate hymen
  • Q52.4 Other congenital malformations of vagina Congenital malformation of vagina NOS Cyst: canal of Nuck, congenital embryonic vaginal
  • Q52.5 Fusion of labia
  • Q52.6 Congenital malformation of clitoris
  • Q52.7 Other congenital malformations of vulva Congenital: absence cyst malformation NOS of vulva
  • Q52.8 Other specified congenital malformations of female genitalia
  • Q52.9 Congenital malformation of female genitalia, unspecified
Q53 Undescended testicle
  • Q53.0 Ectopic testis Unilateral or bilateral ectopic testes
  • Q53.1 Undescended testicle, unilateral
  • Q53.2 Undescended testicle, bilateral
  • Q53.9 Undescended testicle, unspecified Cryptorchism NOS
Q54 Hypospadias

Excl.: epispadias (64.0)

  • Q54.0 Hypospadias, balanic Hypospadias: coronal glandular
  • Q54.1 Hypospadias, penile
  • Q54.2 Hypospadias, penoscrotal
  • Q54.3 Hypospadias, perineal
  • Q54.4 Congenital chordee
  • Q54.8 Other hypospadias
  • Q54.9 Hypospadias, unspecified
Q55 Other congenital malformations of male genital organs

Excl.: congenital hydrocele (P83.5) hypospadias (54.-)

  • Q55.0 Absence and aplasia of testis Monorchism
  • Q55.1 Hypoplasia of testis and scrotum Fusion of testes
  • Q55.2 Other congenital malformations of testis and scrotum Congenital malformation of testis or scrotum NOS Polyorchism Retractile testis Testis migrans
  • Q55.3 Atresia of vas deferens
  • Q55.4 Other congenital malformations of vas deferens, epididymis, seminal vesicles and prostate Absence or aplasia of: prostate spermatic cord Congenital malformation of vas deferens, epididymis, seminal vesicles or prostate NOS
  • Q55.5 Congenital absence and aplasia of penis
  • Q55.6 Other congenital malformations of penis Congenital malformation of penis NOS Curvature of penis (lateral) Hypoplasia of penis
  • Q55.8 Other specified congenital malformations of male genital organs
  • Q55.9 Congenital malformation of male genital organ, unspecified Congenital: anomaly deformity NOS of male genital organ
Q56 Indeterminate sex and pseudohermaphroditism

Excl.: pseudohermaphroditism: female, with adrenocortical disorder (E25.-) male, with androgen resistance (E34.5) with specified chromosomal anomaly (96-99)

  • Q56.0 Hermaphroditism, not elsewhere classified Ovotestis
  • Q56.1 Male pseudohermaphroditism, not elsewhere classified Male pseudohermaphroditism NOS
  • Q56.2 Female pseudohermaphroditism, not elsewhere classified Female pseudohermaphroditism NOS
  • Q56.3 Pseudohermaphroditism, unspecified
  • Q56.4 Indeterminate sex, unspecified Ambiguous genitalia
Please note that this category uses old terminology, that has been replaced elsewhere with "Disorders of Sex Development (DSD)".
World Health Organisation. International Statistical Classification of Diseases and Related Health Problems. (1992) 10th Revision (ICD-10). Geneva: WHO ICD-10 - 2016 Online (English)
Genital Links: Introduction | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Reproductive Cycles | Menstrual Cycle | Male | Testis | Spermatozoa | Penis | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
Historic Embryology - Genital 
1902 The Uro-Genital System | 1904 Ovary and Testis | 1904 Leydig Cells | 1904 Hymen | 1905 Testis vascular | 1912 Urinogenital Organ Development | 1914 Female | 1915 Cowper’s and Bartholin’s Glands | 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
ICD10 - Gastrointestinal | Genital | Renal | Integumentary

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)

Q50 Congenital malformations of ovaries, fallopian tubes and broad ligaments

  • Q50.0 Congenital absence of ovary Excl.: Turner's syndrome (96.-)
  • Q50.1 Developmental ovarian cyst
  • Q50.2 Congenital torsion of ovary
  • Q50.3 Other congenital malformations of ovary Accessory ovary Congenital malformation of ovary NOS Ovarian streak
  • Q50.4 Embryonic cyst of fallopian tube Fimbrial cyst
  • Q50.5 Embryonic cyst of broad ligament Cyst: epoophoron Gartner's duct parovarian
  • Q50.6 Other congenital malformations of fallopian tube and broad ligament Absence Accessory Atresia (of) fallopian tube or broad ligament Congenital malformation of fallopian tube or broad ligament NOS

Q51 Congenital malformations of uterus and cervix

  • Q51.0 Agenesis and aplasia of uterus Congenital absence of uterus
  • Q51.1 Doubling of uterus with doubling of cervix and vagina
  • Q51.2 Other doubling of uterus Doubling of uterus NOS
  • Q51.3 Bicornate uterus
  • Q51.4 Unicornate uterus
  • Q51.5 Agenesis and aplasia of cervix Congenital absence of cervix
  • Q51.6 Embryonic cyst of cervix
  • Q51.7 Congenital fistulae between uterus and digestive and urinary tracts
  • Q51.8 Other congenital malformations of uterus and cervix Hypoplasia of uterus and cervix
  • Q51.9 Congenital malformation of uterus and cervix, unspecified

Q52 Other congenital malformations of female genitalia

  • Q52.0 Congenital absence of vagina
  • Q52.1 Doubling of vagina Septate vagina Excl.: doubling of vagina with doubling of uterus and cervix (51.1)
  • Q52.2 Congenital rectovaginal fistula Excl.: cloaca (43.7)
  • Q52.3 Imperforate hymen
  • Q52.4 Other congenital malformations of vagina Congenital malformation of vagina NOS Cyst: canal of Nuck, congenital embryonic vaginal
  • Q52.5 Fusion of labia
  • Q52.6 Congenital malformation of clitoris
  • Q52.7 Other congenital malformations of vulva Congenital: absence cyst malformation NOS of vulva
  • Q52.8 Other specified congenital malformations of female genitalia
  • Q52.9 Congenital malformation of female genitalia, unspecified

Q53 Undescended testicle

  • Q53.0 Ectopic testis Unilateral or bilateral ectopic testes
  • Q53.1 Undescended testicle, unilateral
  • Q53.2 Undescended testicle, bilateral
  • Q53.9 Undescended testicle, unspecified Cryptorchism NOS

Q54 Hypospadias

Excl.: epispadias (64.0)

  • Q54.0 Hypospadias, balanic Hypospadias: coronal glandular
  • Q54.1 Hypospadias, penile
  • Q54.2 Hypospadias, penoscrotal
  • Q54.3 Hypospadias, perineal
  • Q54.4 Congenital chordee
  • Q54.8 Other hypospadias
  • Q54.9 Hypospadias, unspecified

Q55 Other congenital malformations of male genital organs

Excl.: congenital hydrocele (P83.5) hypospadias (54.-)

  • Q55.0 Absence and aplasia of testis Monorchism
  • Q55.1 Hypoplasia of testis and scrotum Fusion of testes
  • Q55.2 Other congenital malformations of testis and scrotum Congenital malformation of testis or scrotum NOS Polyorchism Retractile testis Testis migrans
  • Q55.3 Atresia of vas deferens
  • Q55.4 Other congenital malformations of vas deferens, epididymis, seminal vesicles and prostate Absence or aplasia of: prostate spermatic cord Congenital malformation of vas deferens, epididymis, seminal vesicles or prostate NOS
  • Q55.5 Congenital absence and aplasia of penis
  • Q55.6 Other congenital malformations of penis Congenital malformation of penis NOS Curvature of penis (lateral) Hypoplasia of penis
  • Q55.8 Other specified congenital malformations of male genital organs
  • Q55.9 Congenital malformation of male genital organ, unspecified Congenital: anomaly deformity NOS of male genital organ

Q56 Indeterminate sex and pseudohermaphroditism

Excl.: pseudohermaphroditism: female, with adrenocortical disorder (E25.-) male, with androgen resistance (E34.5) with specified chromosomal anomaly (96-99)

  • Q56.0 Hermaphroditism, not elsewhere classified Ovotestis
  • Q56.1 Male pseudohermaphroditism, not elsewhere classified Male pseudohermaphroditism NOS
  • Q56.2 Female pseudohermaphroditism, not elsewhere classified Female pseudohermaphroditism NOS
  • Q56.3 Pseudohermaphroditism, unspecified
  • Q56.4 Indeterminate sex, unspecified Ambiguous genitalia

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.[5] See also the Medical Journal of Australia 2009 editorial article.[6]

Previous Terminology New Proposed Terminology
Intersex DSD
Male pseudohermaphrodite, undervirilization of an XY male, and undermasculinization of an XY male 46,XY DSD
Female pseudohermaphrodite, overvirilization of an XX female, and masculinization of an XX female 46,XX DSD
True hermaphrodite Ovotesticular DSD
XX male or XX sex reversal 46,XX testicular DSD
XY sex reversal 46,XY complete gonadal dysgenesis

Sex Chromosome Abnormalities

Trisomy X

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[7]).

Trisomy X karyotype.jpg

Trisomy X karyotype

Links: Trisomy X

Turner Syndrome

The most frequent clinical features of Turner syndrome (45,X) are 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: Student Project - Turner syndrome

Klinefelter's Syndrome

Klinefelter's 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: Student Project - Klinefelter's syndrome

Congenital Adrenal Hyperplasia

  • 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.[8]

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.[9]


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 System - Abnormalities)

Androgen Insensitivity Syndrome

There is a database (Androgen Receptor Gene Mutations) of 1,029 reported androgen receptor mutations.[10] 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[11] and

  • 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

Cryptorchidism
Newborn - cryptorchidism normal birthweight[12]

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.[13] 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.

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.[14] "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 Development

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

  • 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.[2]


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.[15]

  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 [16] 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

Hypospadia

Classification of Hypospadias[17]

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 indivdually or in combination including: familial inheritance, low birth weight, assisted reproductive technology, advanced maternal age, paternal subfertility and endocrine-disrupting chemicals.[18] 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.[19] Infants with hypospadias should not undergo circumcision.


Hypospadia Classification Meatus Opening
Anterior on inferior surface of glans penis
Coronal in balanopenile furrow
Distal on distal third of shaft
Penoscrotal at base of shaft in front of scrotum
Scrotal on scrotum or between the genital swellings
Perineal behind scrotum or genital swellings

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[20] - 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.[21] 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

  1. Burcharth J, Pedersen M, Bisgaard T, Pedersen C, Rosenberg J Nationwide Prevalence of Groin Hernia Repair PLoS ONE 8(1): e54367. doi:10.1371/journal.pone.0054367 (2013) PLoS ONE
  2. 2.0 2.1 [Eisenberg ML, Hsieh MH, Walters RC, Krasnow R, Lipshultz LI. The Relationship between Anogenital Distance, Fatherhood, and Fertility in Adult Men. PLoS One. 2011 May 11;6(5):e18973. PMID:21589916 | PMC3092750 | PLoS One.
  3. S F Ahmed, M Rodie, J Jiang, R O Sinnott The European disorder of sex development registry: a virtual research environment. Sex Dev: 2010, 4(4-5);192-8 PubMed 20501980
  4. R T Scaramuzzo, A Boldrini, S Bertelloni, D Parrini, L Serino, P Ghirri Low testosterone levels in pre-term newborns born small for gestational age. J. Endocrinol. Invest.: 2010, 33(4);215-7 PubMed 20503482
  5. Peter A Lee, Christopher P Houk, S Faisal Ahmed, Ieuan A Hughes, International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics: 2006, 118(2);e488-500 PubMed 16882788 | Pediatrics.
  6. Garry L Warne, Jacqueline K Hewitt Disorders of sex development: current understanding and continuing controversy. Med. J. Aust.: 2009, 190(11);612-3 PubMed 19485836 | Med J Aust.
  7. Nicole R Tartaglia, Susan Howell, Ashley Sutherland, Rebecca Wilson, Lennie Wilson A review of trisomy X (47,XXX). Orphanet J Rare Dis: 2010, 5;8 PubMed 20459843
  8. Saroj Nimkarn, Maria I New Prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Mol. Cell. Endocrinol.: 2009, 300(1-2);192-6 PubMed 19101608
  9. Nicole Reisch, Linda Flade, Michael Scherr, Marietta Rottenkolber, Francesco Pedrosa Gil, Martin Bidlingmaier, Hans Wolff, Hans-Peter Schwarz, Marcus Quinkler, Felix Beuschlein, Martin Reincke High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab.: 2009, 94(5);1665-70 PubMed 19258407 | J Clin Endocrinol Metab.
  10. Bruce Gottlieb, Lenore K Beitel, Abbesha Nadarajah, Miltiadis Paliouras, Mark Trifiro The androgen receptor gene mutations database: 2012 update. Hum. Mutat.: 2012, 33(5);887-94 PubMed 22334387
  11. K A Mooslehner, J D Davies, I A Hughes A cell model for conditional profiling of androgen-receptor-interacting proteins. Int J Endocrinol: 2012, 2012;381824 PubMed 22518120
  12. H E Virtanen, J Toppari Epidemiology and pathogenesis of cryptorchidism. Hum. Reprod. Update: 2007, 14(1);49-58 PubMed 18032558 | Hum Reprod Update.
  13. C R Moore THE BEHAVIOR OF THE GERMINAL EPITHELIUM IN TESTIS GRAFTS AND IN EXPERIMENTAL CRYPTORCHID TESTES (RAT AND GUINEA PIG). Science: 1924, 59(1515);41-4 PubMed 17839834
  14. Christophe Gapany, Peter Frey, Françoise Cachat, Françoise Gudinchet, Patrice Jichlinski, Blaise-Julien Meyrat, Pascal Ramseyer, Gérald Theintz, Bernard Burnand Management of cryptorchidism in children: guidelines. Swiss Med Wkly: 2008, 138(33-34);492-8 PubMed 18726735
  15. Rodolfo Rey Anti-Müllerian hormone in disorders of sex determination and differentiation. Arq Bras Endocrinol Metabol: 2005, 49(1);26-36 PubMed 16544032
  16. Robert J Norman, Ruijin Wu, Marcin T Stankiewicz 4: Polycystic ovary syndrome. Med. J. Aust.: 2004, 180(3);132-7 PubMed 14748678
  17. L S Baskin, K Himes, T Colborn Hypospadias and endocrine disruption: is there a connection? Environ. Health Perspect.: 2001, 109(11);1175-83 PubMed 11713004
  18. L S Baskin, K Himes, T Colborn Hypospadias and endocrine disruption: is there a connection? Environ. Health Perspect.: 2001, 109(11);1175-83 PubMed 11713004
  19. Olof Akre, Heather A Boyd, Martin Ahlgren, Kerstin Wilbrand, Tine Westergaard, Henrik Hjalgrim, Agneta Nordenskjöld, Anders Ekbom, Mads Melbye Maternal and gestational risk factors for hypospadias. Environ. Health Perspect.: 2008, 116(8);1071-6 PubMed 18709149 | PMC2516569
  20. Gholam Hossein Fallahi, Mozhgan Sabbaghian, Manijeh Khalili, Nima Parvaneh, Martin Zenker, Nima Rezaei Novel UBR1 gene mutation in a patient with typical phenotype of Johanson-Blizzard syndrome. Eur. J. Pediatr.: 2011, 170(2);233-5 PubMed 20556423
  21. A M Carragher One hundred years of splenogonadal fusion. Urology: 1990, 35(6);471-5 PubMed 2191479

Reviews



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

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Cite this page: Hill, M.A. 2017 Embryology Genital System - Abnormalities. Retrieved October 21, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Genital_System_-_Abnormalities

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