Patients with abnormal cardiac and kidney function may be more at risk for hemolytic uremic syndrome

The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to diabetic mothers. While most cases are sporadic, there are clearly families who present with multiple involved members.

In some cases, the defect is linked to mutations of the EMX2, SIX3, and Collagen, type IV, alpha 1 genes. Because having a sibling with schizencephaly has been statistically shown to increase risk of the disorder, it is possible that there is a heritable genetic component to the disease.

In utero exposure to cocaine and other street drugs can lead to schizencephaly.

In utero exposure to cocaine and other street drugs can lead to hydranencephaly.

As a recessive genetic condition, both parents must carry the asymptomatic gene and pass it along to their child, a chance of 25 percent. Despite determination of cause, hydranencephaly afflicts both males and females in equal numbers.

There is no known definitive single mechanism that causes colpocephaly. However, researchers believe there are many possible causes of colpocephaly. It is a common symptom of other neurological disorders in newborns, can be caused as a result of shunt treatment of hydrocephalus, developmental disorders in premature infants, due to intrauterine disturbances during pregnancy, genetic disorders, underdevelopment or lack of white matter in the cerebrum, and exposure of the mother and the developing fetus to medications, infections, radiation, or toxic substances. Also, it is usually more common in premature infants than in full-term infants, especially in babies born with hypoxia or lung immaturity.

Some of the central nervous system disorders which are associated with colpocephaly are as follows:

- polymicrogyria

- Periventricular leukomalacia (PVL)

- intraventricular hemorrhage

- Hydrocephalus

- schizencephaly

- microgyria

- microcephaly

- Pierre-Robin syndrome

- Neurofibromatosis

Often colpocephaly occurs as a result of hydrocephalus. Hydrocephalus is the accumulation of cerebrospinal fluid (CSF) in the ventricles or in the subarachnoid space over the brain. The increased pressure due to this condition dilates occipital horns causing colpocephaly.

The most generally accepted theory is that of neuronal migration disorders occurring during the second to fifth months of fetal life. Neuronal migration disorders are caused by abnormal migration, proliferation, and organization of neurons during early brain development. During the seventh week of gestation, neurons start proliferating in the germinal matrix which is located in the subependymal layer of the walls of the lateral ventricles. During the eighth week of gestation, the neurons then start migrating from the germinal zone to cortex along specialized radial glial fibers. Next, neurons organize themselves into layers and form synaptic contacts with other neurons present in the cortex. Under normal conditions, the neurons forming a germinal layer around ventricles migrate to the surface of the brain and form the cerebral cortex and basal ganglia. If this process is abnormal or disturbed it could result in the enlargement of the occipital horns of the lateral ventricles. Common prenatal disturbances that have been shown to disturb the neuronal migration process include the following:

- continuation of oral contraceptives

- exposure to alcohol

- intrauterine malnutrition

- intrauterine infections such as toxoplasmosis

- maternal drug ingestion during early pregnancy such as corticosteroids, salbutamol, and theophylline

Researchers also believe that these factors can cause destruction of neural elements that have previously been normally formed.

It is suggested that the underdevelopment or lack of white matter in the developing fetus could be a cause of colpocephaly. The partial or complete absence of white matter, also known as agenesis of the corpus callosum results in anatomic malformations that can lead to colpocephaly. This starts to occur around the middle of the second month to the fifth month of pregnancy. The lateral ventricles are formed as large cavities of the telencephalic vesicle. The size of the ventricles are decreased in normal development after the formation of the Foramen of Magendie, which decompresses the ventricular cavities. Myelination of the ventricular walls and association fibers of the corpus callosum and the calcarine fissure helps shape the occipital horns. In cases where this developmental process is interrupted, occipital horns are disproportionately enlarged.

Colpocephaly has been associated with chromosomal abnormalities such as trisomy 8 mosaic and trisomy 9 mosaic. A few reports of genetically transmitted colpocephaly are also found in literature. Some of these are of two siblings, monozygotic twins, and non-identical twins. The authors suggest a genetic origin with an autosomal or X-linked recessive inheritance rather than resulting from early prenatal disturbances.

Only a few individuals who did not have fatal kidney and bladder complications are known to have survived beyond birth with this condition.

The prognosis varies widely from case to case, depending on the severity of the symptoms. However, almost all people reported with Aicardi syndrome to date have experienced developmental delay of a significant degree, typically resulting in mild to moderate to profound intellectual disability. The age range of the individuals reported with Aicardi syndrome is from birth to the mid 40s.

There is no cure for this syndrome.

Sirenomelia, alternatively known as Mermaid syndrome, is a rare congenital deformity in which the legs are fused together, giving them the appearance of a mermaid's tail as the nickname suggests.

This condition is found in approximately one out of every 100,000 live births (about as rare as conjoined twins) and is usually fatal within a day or two of birth because of complications associated with abnormal kidney and urinary bladder development and function. More than half the cases of sirenomelia result in stillbirth and this condition is 100 times more likely to occur in identical twins than in single births or fraternal twins. It results from a failure of normal vascular supply from the lower aorta in utero. Maternal diabetes has been associated with caudal regression syndrome and sirenomelia, although a few sources question this association.

VACTERL-H is an expanded form of the VACTERL association that concludes that this diagnosis is a less severe form of sirenomelia. The disorder was formerly thought to be an extreme case of caudal regression syndrome; however, it was reclassified to be considered a separate condition.

Worldwide prevalence of Aicardi Syndrome is estimated at several thousand, with approximately 900 cases reported in the United States.

There is neither a single cause of spina bifida nor any known way to prevent it entirely. However, dietary supplementation with folic acid has been shown to be helpful in reducing the incidence of spina bifida. Sources of folic acid include whole grains, fortified breakfast cereals, dried beans, leaf vegetables and fruits.

Folate fortification of enriched grain products has been mandatory in the United States since 1998. The U.S. Food and Drug Administration, Public Health Agency of Canada and UK recommended amount of folic acid for women of childbearing age and women planning to become pregnant is at least 0.4 mg/day of folic acid from at least three months before conception, and continued for the first 12 weeks of pregnancy.

Women who have already had a baby with spina bifida or other type of neural tube defect, or are taking anticonvulsant medication, should take a higher dose of 4–5 mg/day.

Certain mutations in the gene "VANGL1" have been linked with spina bifida in some families with a history of the condition.

Imperforate anus has an estimated incidence of 1 in 5000 births. It affects boys and girls with similar frequency. However, imperforate anus will present as the low version 90% of the time in females and 50% of the time in males.

Imperforate anus is an occasional complication of sacrococcygeal teratoma.

Spina bifida is sometimes caused by the failure of the neural tube to close during the first month of embryonic development (often before the mother knows she is pregnant). Some forms are known to occur with primary conditions that cause raised central nervous system pressure, raising the possibility of a dual pathogenesis.

In normal circumstances, the closure of the neural tube occurs around the 23rd (rostral closure) and 27th (caudal closure) day after fertilization. However, if something interferes and the tube fails to close properly, a neural tube defect will occur. Medications such as some anticonvulsants, diabetes, obesity, and having a relative with spina bifida can all affect the probability of neural tube malformation.

Extensive evidence from mouse strains with spina bifida indicates that there is sometimes a genetic basis for the condition. Human spina bifida, like other human diseases, such as cancer, hypertension and atherosclerosis (coronary artery disease), likely results from the interaction of multiple genes and environmental factors.

Research has shown the lack of folic acid (folate) is a contributing factor in the pathogenesis of neural tube defects, including spina bifida. Supplementation of the mother's diet with folate can reduce the incidence of neural tube defects by about 70%, and can also decrease the severity of these defects when they occur. It is unknown how or why folic acid has this effect.

Spina bifida does not follow direct patterns of heredity as do muscular dystrophy or haemophilia. Studies show a woman having had one child with a neural tube defect such as spina bifida has about a 3% risk of having another affected child. This risk can be reduced with folic acid supplementation before pregnancy. For the general population, low-dose folic acid supplements are advised (0.4 mg/day).

Neonates with TEF or esophageal atresia are unable to feed properly. Once diagnosed, prompt surgery is required to allow the food intake. Some children do experience problems following TEF surgery; they can develop dysphagia and thoracic problems. Children with TEF can also be born with other abnormalities, most commonly those described in VACTERL association - a group of anomalies which often occur together, including heart, kidney and limb deformities. 6% of babies with TEF also have a laryngeal cleft.

When an individual is born with phocomelia due to drugs or pharmaceuticals, it is known as thalidomide syndrome. The symptoms of thalidomide syndrome are defined by absent or shortened limbs; causing flipper hands and feet. According to Anthony J Perri III, and Sylvia Hsu they can additionally receive:

- Palsy disorder of the face

- Ear and eye abnormalities; resulting in limited/complete loss of hearing or sight

- Gastrointestinal and genitourinary tract disorders

- Ingrown genitalia

- Undeveloped/missing lungs

- Distorted digestive tract, heart, kidney

- disorders to the limbs

The infants that were exposed to thalidomide during development phases had a 40% chance of survival. The McMredie-McBride hypothesis explains that the limbs of the infants become malformed as a result of the thalidomide harming the neural tissue—simply because the neural tissue has such a large impact on formation and development of the limbs.

Young–Madders syndrome, alternatively known as Pseudotrisomy 13 syndrome or holoprosencephaly–polydactyly syndrome, is a genetic disorder resulting from defective and duplicated chromosomes which result in holoprosencephaly, polydactyly, facial malformations and mental retardation, with a significant variance in the severity of symptoms being seen across known cases. Many cases often suffer with several other genetic disorders, and some have presented with hypoplasia, cleft lip, cardiac lesions and other heart defects. In one case in 1991 and another in 2000 the condition was found in siblings who were the product of incest. Many cases are diagnosed prenatally and often in siblings. Cases are almost fatal in the prenatal stage with babies being stillborn.

Though it is now thought that earlier cases were misdiagnosed as other genetic disorders with similar pathology—such as Smith–Lemli–Opitz syndrome—the earliest publicised recognition of the condition as a new, hitherto unclassified, genetic disorder was made by two British doctors in Leicester in 1987. Though they identified the condition, later named for them, they did not identify the genetic anomalies responsible but suspected a link with trisomy 13 due to the similar symptoms. With only one or two occurrences documented towards the end of the decade, a group of eight doctors published a five-patient case-study in 1991 which identified the likely chromosomal factors that caused the condition, similar to but distinct from trisomy 13, and gave it the name 'holoprosencephaly–polydactyly syndrome' based on its two most prolific presenting conditions. Later research showed that the condition could manifest in patients with normal karyotypes, without duplication of the chromosomes, and the most recent genetic research implicates problems with the gene code FBXW11 as a likely cause.

Colpocephaly is usually non-fatal. There has been relatively little research conducted to improve treatments for colpocephaly, and there is no known definitive treatment of colpocephaly yet. Specific treatment depends on associated symptoms and the degree of dysfunction. Anticonvulsant medications can be given to prevent seizure complications, and physical therapy is used to prevent contractures (shrinkage or shortening of muscles) in patients that have limited mobility. Patients can also undergo surgeries for stiff joints to improve motor function. The prognosis for individuals with colpocephaly depends on the severity of the associated conditions and the degree of abnormal brain development.

A rare case of colpocephaly is described in literature which is associated with macrocephaly instead of microcephaly. Increased intracranial pressure was also found in the condition. Similar symptoms (absence of corpus callosum and increased head circumference) were noted as in the case of colpocephaly that is associated with microcephaly. A bi-ventricular peritoneal shunt was performed, which greatly improved the symptoms of the condition. Ventriculo-peritoneal shunts are used to drain the fluid into the peritoneal cavity.

An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies in males and females, that varies from fairly minor lesions to complex anomalies. The cause of ARMs is unknown; the genetic basis of these anomalies is very complex because of their anatomical variability. In 8% of patients genetic factors are clearly associated with ARMs. Anorectal malformation in Currarino syndrome represents the only association for which the gene HLXB9 has been identified.

TBS is an autosomal dominant involving the a mutation of the gene SALL1, which encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. The clinical features of TBS overlap with VATER and VACTERL associations, oculo-auriculo-vertebral (OAV) spectrum, branchio-oto-renal (BOR) syndrome, and Fanconi anemia and other 'anus-hand-ear' syndromes.

Although some symptoms can be life-threatening, many people diagnosed with Townes-Brocks Syndrome live a normal lifespan.

Townes–Brocks syndrome (TBS) is a rare genetic disease that has been described in approximately 200 cases in the published literature. It affects both males and females equally. The condition was first identified in 1972. by Philip L. Townes, MD, PhD, who was at the time a human geneticists and Professor of Pediatrics, and Eric Brocks, MD, who was at the time a medical student, both at the University of Rochester.

It occurs in approximately 1 in 2500 live births.

Congenital esophageal atresia (EA) represents a failure of the esophagus to develop as a continuous passage. Instead, it ends as a blind pouch. Tracheoesophageal fistula (TEF) represents an abnormal opening between the trachea and esophagus. EA and TEF can occur separately or together. EA and TEF are diagnosed in the ICU at birth and treated immediately.

The presence of EA is suspected in an infant with excessive salivation (drooling) and in a newborn with drooling that is frequently accompanied by choking, coughing and sneezing. When fed, these infants swallow normally but begin to cough and struggle as the fluid returns through the nose and mouth. The infant may become cyanotic (turn bluish due to lack of oxygen) and may stop breathing as the overflow of fluid from the blind pouch is aspirated (sucked into) the trachea. The cyanosis is a result of laryngospasm (a protective mechanism that the body has to prevent aspiration into the trachea). Over time respiratory distress will develop.

If any of the above signs/symptoms are noticed, a catheter is gently passed into the esophagus to check for resistance. If resistance is noted, other studies will be done to confirm the diagnosis. A catheter can be inserted and will show up as white on a regular x-ray film to demonstrate the blind pouch ending. Sometimes a small amount of barium (chalk-like liquid) is placed through the mouth to diagnose the problems.

Treatment of EA and TEF is surgery to repair the defect. If EA or TEF is suspected, all oral feedings are stopped and intravenous fluids are started. The infant will be positioned to help drain secretions and decrease the likelihood of aspiration. Babies with EA may sometimes have other problems. Studies will be done to look at the heart, spine and kidneys.

Surgery to repair EA is essential as the baby will not be able to feed and is highly likely to develop pneumonia. Once the baby is in condition for surgery, an incision is made on the side of the chest. The esophagus can usually be sewn together. Following surgery, the baby may be hospitalized for a variable length of time. Care for each infant is individualized.

Its very commonly seen in a newborn with imperforate anus.

When it comes to treatment it is important to differentiate a thumb that needs stability, more web width and function, or a thumb that needs to be replaced by the index finger. Severe thumb hypoplasia is best treated by pollicization of the index finger. Less severe thumb hypoplasia can be reconstructed by first web space release, ligament reconstruction and muscle or tendon transfer.

It has been recommended that pollicization is performed before 12 months, but a long-term study of pollicizations performed between the age of 9 months and 16 years showed no differences in function related to age at operation.

It is important to know that every reconstruction of the thumb never gives a normal thumb, because there is always a decline of function. When a child has a good index finger, wrist and fore-arm the maximum strength of the thumb will be 50% after surgery in comparison with a normal thumb. The less developed the index finger, wrist and fore-arm is, the less strength the reconstructed thumb will have after surgery.

According to National Organization for Rare Disorders (NORD): when phocomelia is transmitted [in its familial genetic form] it is seen as an autosomal recessive trait and the mutation is linked to chromosome 8.

A study of Roberts Syndrome, a genetic disorder showing similar symptoms to phocomelia, has shed light on the possible causes. An individual afflicted with Roberts Syndrome will have chromosome copies that do not connect at the centromeres, making them unable to line up accordingly. As a result, the newly made cells contain an excess or reduced number of chromosomes. In both Roberts Syndrome and phocomelia the cells cease to develop, or die, preventing proper development of the limbs, eyes, brain, palate, or other structures.

This birth defect arises in the fourth fetal week, when the trachea and esophagus should begin to separate from each other.

It can be associated with disorders of the tracheoesophageal septum.