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 and other various abnormalities that range from cloaca 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.

Prenatal Diagnosis:

- Aymé, "et al." (1989) reported prenatal diagnosis of Fryns syndrome by sonography between 24 and 27 weeks.

- Manouvrier-Hanu et al. (1996) described the prenatal diagnosis of Fryns syndrome by ultrasonographic detection of diaphragmatic hernia and cystic hygroma. The diagnosis was confirmed after termination of the pregnancy. The fetus also had 2 erupted incisors; natal teeth had not been mentioned in other cases of Fryns syndrome.

Differential Diagnosis:

- McPherson et al. (1993) noted the phenotypic overlap between Fryns syndrome and the Pallister–Killian syndrome (601803), which is a dysmorphic syndrome with tissue-specific mosaicism of tetrasomy 12p.

- Veldman et al. (2002) discussed the differentiation between Fryns syndrome and Pallister–Killian syndrome, noting that differentiation is important to genetic counseling because Fryns syndrome is an autosomal recessive disorder and Pallister–Killian syndrome is usually a sporadic chromosomal aberration. However, discrimination may be difficult due to the phenotypic similarity. In fact, in some infants with 'coarse face,' acral hypoplasia, and internal anomalies, the initial diagnosis of Fryns syndrome had to be changed because mosaicism of isochromosome 12p was detected in fibroblast cultures or kidney tissue. Although congenital diaphragmatic hernia is a common finding in both syndromes, bilateral congenital diaphragmatic hernia had been reported only in patients with Fryns syndrome until the report of the patient with Pallister–Killian syndrome by Veldman et al. (2002).

- Slavotinek (2004) reviewed the phenotypes of 52 reported cases of Fryns syndrome and reevaluated the diagnostic guidelines. She concluded that congenital diaphragmatic hernia and distal limb hypoplasia are strongly suggestive of Fryns syndrome, with other diagnostically relevant findings including pulmonary hypoplasia, craniofacial dysmorphism, polyhydramnios, and orofacial clefting. Slavotinek (2004) stated that other distinctive anomalies not mentioned in previous guidelines include ventricular dilatation or hydrocephalus, agenesis of the corpus callosum, abnormalities of the aorta, dilatation of the ureters, proximal thumbs, and broad clavicles.

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, 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 fill with 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.

When an infant is born with PSH, the most difficult management decision has often been the sex assignment, since genitalia with this degree of ambiguity do not resemble either sex very well with respect to looks or function. Many infants with PPHS have been assigned and raised as female despite presence of testes and XY chromosomes.

Nearly all parents of infants with PPSH are offered surgical reconstruction, to either further masculinize or feminize the external genitalia.

Treatment with testosterone postnatally does not close the urethra or change the malformation, but in some cases may enlarge the penis slightly.

Abdominal ultrasound is of some benefit, but not diagnostic. Features that suggest posterior urethral valves are bilateral hydronephrosis, a thickened bladder wall with thickened smooth muscle trabeculations, and bladder diverticula.

Voiding cystourethrogram (VCUG) is more specific for the diagnosis. Normal "plicae circularis" are variable in appearance and often not seen on normal VCUGs. PUV on voiding cystourethrogram is characterized by an abrupt tapering of urethral caliber near the verumontanum, with the specific level depending on the developmental variant. Vesicoureteral reflux is also seen in over 50% of cases. Very often the posterior urethra maybe dilated thus making the abrupt narrowing more obvious. the bladder wall may show trabeculations or sacculations or even diverticuli.

Diagnosis can also be made by cystoscopy, where a small camera is inserted into the urethra for direct visualization of the posteriorly positioned valve. A limitation of this technique is that posterior valve tissue is translucent and can be pushed against the wall of the urethra by inflowing irrigation fluid, making it difficult to visualize. Cystoscopy may also demonstrate the bladder changes.

Centers in Europe and Japan have also had excellent results with cystosonography, although it has not been approved for use in the United States yet.

In France, Aymé, "et al." (1989) estimated the prevalence of Fryns syndrome to be 0.7 per 10,000 births based on the diagnosis of 6 cases in a series of 112,276 consecutive births (live births and perinatal deaths).

MCDK is usually diagnosed by ultrasound examination before birth. Mean age at the time of antenatal diagnosis is about 28 weeks A microscopic analysis of urine in individuals with probable multicystic dysplastic kidney should be done. One meta-analysis demonstrated that unilateral MCDK occurs more frequently in males and the greater percentage of MCKD occur on the left side of the body.

Diagnosis is based on physical examination including radiographs of the hands and feet and imaging studies of the kidneys, bladder, and female reproductive tract. HOXA13 is the only gene known to be associated with HFGS. Approximately 60% of mutations are polyalanine expansions. Molecular genetic testing is clinically available.

The prognostic outcomes for this type of cloaca are good for bowel control and urinary function. The surgical repair for this type of cloaca can usually be done by performing posterior sagittal approach without opening of the abdomen. A common channel longer than 3 cm in length usually has poor sphincter muscles and a poor sacrum, suggesting a prognostic outcome for bowel control and urinary function to be less likely. Common channels longer than 3 cm are generally considered more complex and more technically challenging in surgical repair.

It is considered a form of 5-alpha-reductase deficiency involving SRD5A2.

Additional findings that may be present in HFGS according to the latest research are:

- Limited metacarpophalangeal flexion of the thumb or limited ability to oppose the thumb and fifth finger

- Hypoplastic thenar eminences

- Medial deviation of the great toe (hallux varus), a useful diagnostic sign when present

- Small great toenail

- Fifth-finger clinodactyly, secondary to a shortened middle phalanx

- Short feet

- Altered dermatoglyphics of the hands; when present, primarily involving distal placement of the axial triradius, lack of thenar or hypothenar patterning, low arches on the thumbs, thin ulnar loops (deficiency of radial loops and whorls), and a greatly reduced ridge count on the fingers

Radiographic findings

- Hypoplasia of the distal phalanx and first metacarpal of the thumbs and great toes

- Pointed distal phalanges of the thumb

- Lack of normal tufting of the distal phalanges of the great toes

- Fusions of the cuneiform to other tarsal bones or trapezium-scaphoid fusion of the carpals

- Short calcaneus

- Occasional bony fusions of the middle and distal phalanges of the second, third, fourth, or fifth toes

- Delayed carpal or tarsal maturation

- Metacarpophalangeal profile reflecting shortening of the first metacarpal, the first and second phalanges, and the second phalanx of the second and fifth digits

Urogenital Defects

Females may have the following:

- Vesicoureteral reflux secondary to ureteric incompetence

- Ectopic ureteral orifices

- Trigonal hypoplasia

- Hypospadiac urethra

- Subsymphyseal epispadias

- Patulous urethra

- Urinary incontinence (related to structural anomalies and weakness of the bladder sphincter muscle)

- Small hymenal opening

- Various degrees of incomplete Müllerian fusion with or without two cervices or a longitudinal vaginal septum

Males may have the following:

- Retrograde ejaculation (related to structural anomalies and weakness of the bladder sphincter muscle)

Lymphatic malformations may be detected in the human fetus by ultrasound if they are of sufficient size. Detection of a cystic malformation may prompt further investigation, such as amniocentesis, in order to evaluate for genetic abnormalities in the fetus. Lymphatic malformations may be discovered postnatally or in older children/adults, and most commonly present as a mass or as an incidental finding during medical imaging.

Verification of the diagnosis may require more testing, as there are multiple cystic masses that arise in children. Imaging, such as ultrasound or MRI, may provide more information as to the size and extent of the lesion.

Vesicovaginal fistulae are typically repaired either transvaginally or laparoscopically, although patients who have had multiple transvaginal procedures sometimes attempt a final repair through a large abdominal incision, or laparotomy.

The laparoscopic (minimally invasive) approach to VVF repair has become more prevalent due to its greater visualization, higher success rate, and lower rate of complications.

The main treatment for isolated epispadias is a comprehensive surgical repair of the genito-urinary area usually during the first 7 years of life, including reconstruction of the urethra, closure of the penile shaft and mobilisation of the corpora. The most popular and successful technique is known as the modified Cantwell-Ransley approach. In recent decades however increasing success has been achieved with the complete penile disassembly technique despite its association with greater and more serious risk of damage.

Alternatively, female genital diseases can be more strictly classified by location of the disease, which, in turn, can be broadly divided between diseases that affect the female internal genitalia and those that affect the female external genitalia.

Malformations can be congenital. They are classified by location of the malformation, such as uterine malformation.

Besides a physical examination, the physician will need imaging techniques to determine the character of the malformation: gynecologic ultrasonography, pelvic MRI, or hysterosalpingography. A hysterosalpingogram is not considered as useful due to the inability of the technique to evaluate the exterior contour of the uterus and distinguish between a bicornuate and septate uterus.

In addition, laparoscopy and/or hysteroscopy may be indicated.

In some patients the vaginal development may be affected.

Once the diagnosis of polymicrogyria has been established in an individual, the following approach can be used for discussion of prognosis:

A pregnancy history should be sought, with particular regard to infections, trauma, multiple gestations, and other documented problems. Screening for the common congenital infections associated with polymicrogyria with standard TORCH testing may be appropriate. Other specific tests targeting individual neurometabolic disorders can be obtained if clinically suggested.

The following may help in determining a genetic etiology:

Family history

It is important to ask for the presence of neurologic problems in family members, including seizures, cognitive delay, motor impairment, pseudobulbar signs, and focal weakness because many affected family members, particularly those who are older, may not have had MRI performed, even if these problems came to medical attention. In addition, although most individuals with polymicrogyria do present with neurologic difficulties in infancy, childhood, or adulthood, those with mild forms may have no obvious deficit or only minor manifestations, such as a simple lisp or isolated learning disability. Therefore, if a familial polymicrogyria syndrome is suspected, it may be reasonable to perform MRI on relatives who are asymptomatic or have what appear to be minor findings. The presence of consanguinity in a child's parents may suggest an autosomal recessive familial polymicrogyria syndrome.

Physical examination

A general physical examination of the proband may identify associated craniofacial, musculoskeletal, or visceral malformations that could indicate a particular syndrome. Neurologic examination should assess cognitive and mental abilities, cranial nerve function, motor function, deep tendon reflexes, sensory function, coordination, and gait (if appropriate).

Genetic testing

Three dimensional (3D) T1W, Axial, coronal, sagittal imaging is excellent for differentiation between gray matter and white matter acquisition of high-resolution anatomic information.T2W, Axial and coronal imaging for acquisition of high-resolution anatomic information; delineation of cortex, white matter, and gray matter nuclei. Diffusion tensor, axial imaging is used for evaluation of white matter microstructural integrity, identification of white matter tracts. CISS, axial + MPR imaging for evaluation of cerebellar folia, cranial nerves, ventricles, and foramina. Susceptibility weighted axial scan for Identification and characterization of hemorrhage, blood products, calcification, and iron accumulation.

Diagnosis of a female with cloaca should be suspected in a female born with an imperforate anus and small looking genitalia. The diagnosis can be made clinically. Failure to identify a cloaca as being present in a newborn may be dangerous, as more than 90% have associated urological problems. The goal for treatment of a female born with cloaca is to achieve bowel control, urinary control, and sexual function, which includes menstruation, sexual intercourse, and possibly pregnancy. Cloacas probably occur in 1 in 20,000 live births.

If suspected antenatally, a consultation with a paediatric surgeon/ paediatric urologist maybe indicated to evaluate the risk and consider treatment options.

Treatment is by endoscopic valve ablation. Fetal surgery is a high risk procedure reserved for cases with severe oligohydramnios, to try to limit the associated lung underdevelopment, or pulmonary hypoplasia, that is seen at birth in these patients. The risks of fetal surgery are significant and include limb entrapment, abdominal injury, and fetal or maternal death. Specific procedures for "in utero" intervention include infusions of amniotic fluid, serial bladder aspiration, and creating a connection between the amniotic sac and the fetal bladder, or vesicoamniotic shunt.

There are three specific endoscopic treatments of posterior urethral valves:

- Vesicostomy followed by valve ablation - a stoma, or hole, is made in the urinary bladder, also known as "low diversion", after which the valve is ablated and the stoma is closed.

- Pyelostomy followed by valve ablation - stoma is made in the pelvis of the kidney as a slightly "high diversion", after which the valve is ablated and the stoma is closed

- Primary (transurethral) valve ablation - the valve is removed through the urethra without creation of a stoma

The standard treatment is primary (transurethral) ablation of the valves. Urinary diversion is used in selected cases, and its benefit is disputed.

Following surgery, the follow-up in patients with posterior urethral valve syndrome is long term, and often requires a multidisciplinary effort between paediatric surgeons/ paediatric urologists, pulmonologists, neonatologists, radiologists and the family of the patient. Care must be taken to promote proper bladder compliance and renal function, as well as to monitor and treat the significant lung underdevelopment that can accompany the disorder. Definitive treatment may also be indicated for the vesico-ureteral reflux.

Even with successful surgery, patients may have long-term problems with:

- incontinence, where serious usually treated with some form of continent urinary diversion such as the Mitrofanoff

- depression and psycho-social complications

- sexual dysfunction

Identification of 45,X/46,XY karyotype has significant clinical implications due to known effects on growth, hormonal balance, gonadal development and histology. 45,X/46,XY is diagnosed by examining the chromosomes in a blood sample.

The age of diagnosis varies depending on manifestations of disease prompting reason for cytogenetic testing. Many patients are diagnosed prenatally due to fetal factors (increased nuchal fold, or abnormal levels of serum), maternal age or abnormal ultrasounds, while others will be diagnosed postnatal due to external genital malformation. It is not uncommon for patients to be diagnosed later in life due to short stature or delayed puberty, or a combination of both.

45,X/46,XY mosaicism can be detected prenatally through amniocentesis however, it was determined that the proportion of 45,X cells in the amniotic fluid cannot predict any phenotypic outcomes, often making prenatal genetic counselling difficult.

MCDK is not treatable. However, the patient is observed periodically for the first few years during which ultrasounds are generally taken to ensure the healthy kidney is functioning properly and that the unhealthy kidney is not causing adverse effects. In severe cases MCDK can lead to neonatal fatality (in bilateral cases), however in unilateral cases the prognosis might be better (it would be dependent on associated anomalies).

The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy.

Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas et al. (1986) also emphasized the occurrence of the cryptophthalmos syndrome without cryptophthalmos and proposed diagnostic criteria for Fraser syndrome. Major criteria consisted of cryptophthalmos, syndactyly, abnormal genitalia, and positive family history. Minor criteria were congenital malformation of the nose, ears, or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation. Diagnosis was based on the presence of at least 2 major and 1 minor criteria, or 1 major and 4 minor criteria.

Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome. Serville et al. (1989) demonstrated the feasibility of ultrasonographic diagnosis of the Fraser syndrome at 18 weeks' gestation. They suggested that the diagnosis could be made if 2 of the following signs are present: obstructive uropathy, microphthalmia, syndactyly, and oligohydramnios. Schauer et al. (1990) made the diagnosis at 18.5 weeks' gestation on the basis of sonography. Both the female fetus and the phenotypically normal father had a chromosome anomaly: inv(9)(p11q21). An earlier born infant had Fraser syndrome and the same chromosome 9 inversion.

Van Haelst et al. (2007) provided a revision of the diagnostic criteria for Fraser syndrome according to Thomas et al. (1986) through the addition of airway tract and urinary tract anomalies to the major criteria and removal of mental retardation and clefting as criteria. Major criteria included syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. Cleft lip and/or palate, cardiac malformations, musculoskeletal anomalies, and mental retardation were considered uncommon. Van Haelst et al. (2007) suggested that the diagnosis of Fraser syndrome can be made if either 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria are present in a patient.