Vaginal atresia is a condition in which the

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...

is abnormally closed or absent. The main causes can either be complete

vaginal hypoplasia Vaginal hypoplasia is the underdevelopment or incomplete development of the vagina. It is a birth defect or congenital abnormality of the female genitourinary system. Signs and symptoms Vaginal hypoplasia can vary in severity from being smaller t ...

, or a vaginal obstruction, often caused by an

imperforate hymen An imperforate hymen is a congenital disorder where a hymen without an opening completely obstructs the vagina. It is caused by a failure of the hymen to perforate during Prenatal development, fetal development. It is most often diagnosed in adole ...

or, less commonly, a

transverse vaginal septum A vaginal septum is a vaginal anomaly that is partition within the vagina; such a septum could be either longitudinal or transverse. In some affected women, the septum is partial or does not extend the length or width of the vagina. Pain during ...

. It results in uterovaginal outflow tract obstruction. This condition does not usually occur by itself within an individual, but coupled with other developmental disorders within the female. The disorders that are usually coupled with a female who has vaginal atresia are Mayer-Rokitansky-Küster-Hauser syndrome, Bardet-Biedl syndrome, or

Fraser syndrome Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder, identified by several developmental anomalies. Fraser syndrome is named for t ...

. One out of every 5,000 women have this abnormality.

Symptoms and signs

Symptoms and signs in the newborn can be

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

abdominal mass An abdominal mass is any localized enlargement or swelling in the human abdomen. Depending on its location, the abdominal mass may be caused by an enlarged liver (hepatomegaly), enlarged spleen (splenomegaly), protruding kidney, a pancreatic mass, ...

, and

respiratory distress Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...

. Other abdominopelvic or perineal congenital anomalies frequently prompt radiographic evaluation in the newborn, resulting in a diagnosis of coincident vaginal atresia. Symptoms for vaginal atresia include cyclical abdominal pain, the inability to start having menstrual cycles, a small pouch or dimple where a vaginal opening should be, and pelvic mass when the upper vagina becomes filled with menstrual blood. Signs and symptoms of vaginal atresia or vaginal agenesis can often go unnoticed in females until they reach the age of menstruation. Women may also experience some form of abdominal pain or cramping.

Causes

The cause for vaginal atresia is unknown. Typically, the creation of the vaginal canal is completed within the fetus by the 20th week of

gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...

. Researchers believe in patients with vaginal atresia, tubes known as the

Müllerian ducts Paramesonephric ducts (or Müllerian ducts) are paired ducts of the embryo that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive urogenital sinus. In the female, they will develop to form the fal ...

do not develop correctly within the first 20 weeks of gestation/pregnancy. Typically, one of these ducts develops in the

fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...

s while the other ducts develop into the vagina and uterus. Vaginal atresia is found to occur when the urogenital sinus does not contribute to the formation of the lower portion of the vagina. As previously mentioned, there are other disorders or syndromes that are found in conjunction with individuals living with vaginal atresia. These disorders are:

Rokitansky-Mayer-Küster-Hauser syndrome

Rokitansky-Mayer-Küster-Hauser syndrome is a disorder in females that causes the uterus and vagina to be absent or underdeveloped. Those born with this disorder are considered to be genetic female and have a 46XX chromosomes. Kidney anomalies often accompany this disorder as well. Also referred to as

Müllerian agenesis Müllerian agenesis, also known as Müllerian aplasia, vaginal agenesis, or Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome), is a congenital malformation characterized by a failure of the Müllerian ducts to develop, resulting in a missi ...

, vaginal agenesis, or Müllerian aplasia, this disorder affects 1 in every 4,000-5,000 females. A cloacal malformation often accompanies this disorder, which is the surgical treatment that incorporates several vaginal replacement techniques. This disorder is caused by an implication in the ''

WNT4 WNT4 is a secreted protein that in humans is encoded by the ''Wnt4'' gene, found on chromosome 1. It promotes female sex development and represses male sex development. Loss of function can have serious consequences, such as female to male sex rev ...

'' protein coding gene, which is found on the short arm (p) of

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which ar ...

. A genetic mutation occurs causing a substitution of leucine to proline residue at position 12 on the amino acid in the WNT4 protein. Essentially, this will cause a reduction in the intranuclear levels of β catenin. Additionally, steroidogenic enzymes such as

17α-hydroxylase Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously expr ...

and 3β-hydroxysteriod dehydrogenase are inhibited because of this mutation, which leads to an excess amount to

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...

in the system. As the ''WNT4'' gene is essential for developing a protein that is essential for female sex development, the

Müllerian duct Paramesonephric ducts (or Müllerian ducts) are paired ducts of the embryo that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive urogenital sinus. In the female, they will develop to form the fal ...

is either absent or deformed when this gene is not present. The development of the female reproductive system may be disrupted in the absence of the WNT4 protein's regulation. Abnormal androgen production is also induced, eventually leading to hyperandrogenism and Müllerian aplasia.

Bardet-Biedl Syndrome

Bardet-Biedl syndrome (BBS) is a

ciliopathic A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...

human genetic disorder that can affect various parts of the body. Parts of the urogenital system where the effects of BBS are seen include:

ectopic urethra Ectopic ureter (or ureteral ectopia) is a medical condition where the ureter, rather than terminating at the urinary bladder, terminates at a different site. In males this site is usually the urethra, in females this is usually the urethra or vag ...

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

uterus duplex A uterine malformation is a type of female genital malformation resulting from an abnormal development of the Müllerian duct(s) during embryogenesis. Symptoms range from amenorrhea, infertility, recurrent pregnancy loss, and pain, to normal fun ...

hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...

septate vagina A uterine malformation is a type of female genital malformation resulting from an abnormal development of the Müllerian duct(s) during embryogenesis. Symptoms range from amenorrhea, infertility, recurrent pregnancy loss, and pain, to normal funct ...

, and

hypoplasia Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...

. Some of the common characteristics associated with this syndrome include intellectual disorders, loss of vision, kidney problems, and obesity. The mechanism that causes BBS is still remains unclear. Mutations in more than 20 genes can cause BBS and is an inherited recessive condition. Some of the gene mutations that occur in BBS are listed below: ''

BBS1 Bardet–Biedl syndrome 1 protein is a protein that in humans is encoded by the ''BBS1'' gene. BBS1 is part of the BBSome complex, which required for ciliogenesis. Mutations in this gene have been observed in patients with the major form (type 1) ...

BBS2 Bardet–Biedl syndrome 2 protein is a protein that in humans is encoded by the ''BBS2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generat ...

, ARL6 (BBS3),

BBS4 Bardet–Biedl syndrome 4 is a protein that in humans is encoded by the ''BBS4'' gene. This gene encodes a protein which contains tetratricopeptide repeats (TPR), similar to O-linked N-acetylglucosamine transferase. Mutations in this gene have be ...

BBS5 Bardet–Biedl syndrome 5 protein is a protein that in humans is encoded by the ''BBS5'' gene. This gene encodes a protein that has been directly linked to Bardet–Biedl syndrome. The primary features of this syndrome include retinal dystrophy, ...

, MKKS (BBS6),

BBS7 Bardet–Biedl syndrome 7 is a protein that in humans is encoded by the ''BBS7'' gene. Mutations in this gene are associated with the Bardet–Biedl syndrome Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produce ...

, TTC8 (BBS8),

BBS9 Bardet–Biedl syndrome 9 is a protein that in humans is encoded by the ''BBS9'' gene. The expression of the Bardet–Biedl syndrome 9 protein is downregulated by parathyroid hormone in osteoblastic cells, and therefore, is thought to be involved ...

, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), IFT27 (BBS19), IFT72 (BBS20)'', and ''C8ORF37(BBS21'') The majority of the genes that are related to BBS encode proteins which are called cilia and basal bodies, which are related structures.

Fraser Syndrome

is a disorder that affects the development of the child prior to birth. Infants born with Fraser syndrome often have eyes that are malformed and completely covered by skin. Also the child is born with fingers and toes that are fused together along with abnormalities within the urine tract. As this disorder relates to vaginal atresia, infants born with Fraser syndrome are also born with malformations in their genitals.

McKusick-Kaufman syndrome

A female with McKusick-Kaufman syndrome has vaginal atresia that is often present with imperforate anus, heart defects, hydrometrocolpos, and/or polydactyly, The female will still develop secondary sexual characteristics.

Mechanism

The exact mechanism for vaginal atresia is not well known, as specific molecular mechanisms which lead to the closing or absence of the vagina are unclear. There are various pathways that may support or restrict regular vaginal development. Research has shown that changing factors may also include

paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse ove ...

and autocrine signals and changes in the basis of developing organs. Specific patterns of genetic transmission have not been identified for this condition. Normal reproductive organ production requires timely coordination of the following systems: external genitalia, internal ductal system, and gonadal structure. The abnormal development of the vagina results in an incomplete unit (low, mid, high transverse septum), failure of epithelium degeneration (

), and vaginal atresia. According to a number of medical professionals, timely coordination of interdependent systems is required for normal reproductive organ development in both males and females. The description of vaginal atresia mechanism can be explained in several steps of development of the uterovaginal canal per the information provided by these medical professionals. These interdependent systems are external genitalia,

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

al structures, and internal

ductal Lafarge is a French industrial company specialising in cement, construction aggregates, and concrete. It is the world's largest cement manufacturer. It was founded in 1833 by Joseph-Auguste Pavin de Lafarge and is a part of the Holcim Group. ...

system. The absence of

s, Müllerian-inhibiting substance (MIS), and

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...

causes the continuous differentiation of the

with reversion of the wolffian ducts in the female

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

. The Müllerian duct will then elongate to reach the

urogenital sinus The urogenital sinus is a part of the human body only present in the development of the urinary and reproductive organs. It is the ventral part of the cloaca, formed after the cloaca separates from the anal canal during the fourth to seventh we ...

within 9 weeks of

; this forms the uterovaginal canal. By 15–26 weeks of gestation,

cephalic A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple animals may ...

growth of the sinovaginal bulb is completed. The

vaginal plate In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hym ...

is also formed from the fusion of vaginal cord with the sinovaginal bulb. The formation of the uterovaginal canal is thought to occur from the caudal to the cephalic portion, all while the urogenital sinus is used to create the

epithelial lining Epithelium or epithelial tissue is one of the four basic types of animal Tissue (biology), tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed Cell (biology), ...

. Development of the vagina is completed by the fifth month of gestation. While the

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

that surrounds the structures transitions into

musculature Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...

of the genital tract, the

s are formed via the cephalic remnants of the Müllerian duct. This developmental process attributes to the process of how proper vaginal development takes place. Failure of the septum to regress between the fused Müllerian ducts results in a

septate uterus A uterine septum is a form of a congenital malformation where the uterine cavity is partitioned by a longitudinal septum; the outside of the uterus has a normal typical shape. The wedge-like partition may involve only the superior part of the cavi ...

. The incomplete fusion of the Müllerian ducts attributes to the formation of

arcuate ''Arcuate'' (Latin for "curved") can refer to: Anatomy * Arcuate fasciculus * Arcuate line (disambiguation) * Arcuate artery (disambiguation), several arteries * Arcuate nucleus * Arcuate nucleus (medulla) * Arcuate ligaments of the diaphragm * A ...

, bicornuate, or didelphid uteri. Females who have both Rokitansky-Mayer-Küster-Hauser syndrome and uterovaginal atresia are theorized to have a failing caudal development within the Müllerian ducts. Variations of transverse vaginal septum might be described by the malfunctions at the level of the vaginal plate. Though the Müllerian and urogenital sinuses play a huge role in the derivation of the vagina, it is unclear how much of a role each of these play normal vaginal development.

Diagnosis

Vaginal atresia can sometimes be diagnosed by physical examination soon after birth. A child with vaginal atresia often has other congenital abnormalities and other tests such as X-ray and tests to evaluate the kidneys are done. Findings in adolescents may include abdominal pain, difficulty voiding, and backache, but most present with amenorrhea. Difficulties with sexual intercourse can suggest atresia. In the event that the condition is not caught shortly after birth, vaginal atresia becomes more evident when no menstrual cycle is occurs. If vaginal atresia is suspected by the doctor, a

blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...

may also be request for any of the previously mentioned syndromes, a

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI) test, or an

ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...

. A regular evaluation of children born with an

imperforate anus An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unknow ...

anorectal malformation An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unkno ...

should be paired with the assessment of the results from these tests. Agenesia de vagina2

Treatment

There are several methods of treatment for individuals with vaginal atresia. The first method of treatment that is recommended would be self-dilation of the vagina. A doctor may first recommend that the patient first attempts to create a vagina themselves through the process self-dilation. The self dilation technique consists of using

vaginal dilator A vaginal dilator (sometimes called a vaginal trainer) is an instrument used to gently stretch the vagina. They are used when the vagina has become narrowed ( vaginal stenosis), such as after brachytherapy for gynecologic cancers, and as therapy ...

s, which are small round tubes that vary in size and are similar in size and shape to

tampon A tampon is a feminine hygiene, menstrual product designed to absorb blood and vaginal secretions by insertion into the vagina during menstruation. Unlike a Sanitary napkin, pad, it is placed internally, inside of the vaginal canal. Once inser ...

s. Vaginal dilators may be pressed alongside the vaginal area on a regular basis in order to further open the vaginal canal. Frank's procedure is a technique that used a progressive series of vaginal dilators that are inserted into the dimple of the vagina while using pressure. This will widen any space that exists between the bladder and the rectum. Frank's procedure can be performed directly by the patient, therefore requiring no surgery or anesthesia. The procedure/technique can take months to complete, with regular compliance necessary. The overall success rate for females who use Frank's procedure is 80%. If this procedure does not work, then surgery would be the next method of treatment. Another alternative form of treatment would be surgery, or the creation of a new vagina.

Prognosis

The prognosis for vaginal atresia is one that is complicated. There are variations in patients' anatomic findings as well as an absence in consistent surgical techniques which makes it difficult to give a prognosis for this condition. Along with other conditions that give rise to an abnormal perineum (i.e.

ambiguous genitalia Intersex people are individuals born with any of several sex characteristics including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical bina ...

and other various abnormalities that range from

cloaca In animal anatomy, a cloaca ( ), plural cloacae ( or ), is the posterior orifice that serves as the only opening for the digestive, reproductive, and urinary tracts (if present) of many vertebrate animals. All amphibians, reptiles and birds, a ...

to urogenital sinus), individuals with vaginal atresia often report reconstruction as an outcome of treatment. Due to this, it is difficult to compare outcomes between individuals with vaginal atresia.

Rokitansky-Mayer-Küster-Hauser Syndrome

Fertility options for girls and women with Rokitansky-Mayer-Küster-Hauser syndrome has a bit more information. Girls and women who are born without a complete vagina, but still have a regular sized uterus more than likely will be able to become pregnant and have a baby. However, if the female is born with a tiny uterus, or without a uterus, they will not be able to have a baby. As the ovaries may be normal in this case, the egg may be fertilized with a donor's or partner's sperm. In this case,

surrogacy Surrogacy is an arrangement, often supported by a legal agreement, whereby a woman agrees to delivery/labour for another person or people, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnan ...

, would be an option where there will be a gestational carrier to carry the pregnancy for the couple. Adoption may also be an option for females with Rokitansky-Mayer-Küster-Hauser syndrome. Another possibility could be uterine transplants, however this a new and developing form of treatment. Fertility options are being researched daily, so there can always be a new method available. Any pain associated with Rokitansky-Mayer-Küster-Hauser syndrome comes from menstruation related cramping and can be treated with several ways. Individuals with this syndrome may be born with a uterine remnant (tiny uterus), which can become filled with blood in the pelvic cavity causing pain. A medical professional can assess the severity of having a uterine remnant within each patient to determine if removal of the uterus is necessary.

Bardet-Biedl Syndrome

There is no cure available for individuals with Bardet-Biedl Syndrome; however, there are methods of treatment for some of the signs and symptoms within each individual. Corrective surgery of malformation related to the disorder may be an option for treatment. Genetic counseling can also be beneficial to families with this disorder.

References

{{Reflist Congenital disorders of female genital organs Vagina Pediatric gynecology