Recent research has found that Dandy–Walker syndrome often occurs in patients with PHACES syndrome.

In a newborn boy thought to have Fryns syndrome, Clark and Fenner-Gonzales (1989) found mosaicism for a tandem duplication of 1q24-q31.2. They suggested that the gene for this disorder is located in that region. However, de Jong et al. (1989), Krassikoff and Sekhon (1990), and Dean et al. (1991) found possible Fryns syndrome associated with anomalies of chromosome 15, chromosome 6, chromosome 8(human)and chromosome 22, respectively. Thus, these cases may all represent mimics of the mendelian syndrome and have no significance as to the location of the gene for the recessive disorder.

By array CGH, Slavotinek et al. (2005) screened patients with DIH and additional phenotypic anomalies consistent with Fryns syndrome for cryptic chromosomal aberrations. They identified submicroscopic chromosome deletions in 3 probands who had previously been diagnosed with Fryns syndrome and had normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving 15q26.2 (see 142340), and 1 male infant had a deletion in band 8p23.1 (see 222400).

Until recently, the medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause (genotype) despite the widely varying set of medical characteristics (phenotype) that are clinically visible in the disorders. Dandy–Walker syndrome is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell, organelles which are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.

Genetic associations of the condition are being investigated.

In utero exposure to cocaine and other street drugs can lead to agenesis of corpus callosum.

The prognosis of this developmental disorder is highly based on the underlying disorder. Cerebellar hypoplasia may be progressive or static in nature. Some cerebellar hypoplasia resulting from congenital brain abnormalities/malformations are not progressive. Progressive cerebellar hypoplasia is known for having poor prognosis, but in cases where this disorder is static, prognosis is better.

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.

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).

Until recently, the medical literature did not indicate a connection among many genetic disorders, both genetic syndromes and genetic diseases, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause despite the widely varying symptoms apparent on clinical examination. Agenesis of the corpus callosum is one such disease, part of an emerging class of diseases called ciliopathies. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell organelles that are present in many cellular types throughout the human body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome, and some forms of retinal degeneration.

Ear agenesis is a medical condition in which people are born without ears.

Because the middle and inner ears are necessary for hearing, people with complete agenesis of the ears are totally deaf. Minor agenesis that affects only the visible parts of the outer ear, which may be called microtia, typically produces cosmetic concerns and perhaps hearing impairment if the opening to the ear canal is blocked, but not deafness.

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.

Because pachygyria is a structural defect no treatments are currently available other than symptomatic treatments, especially for associated seizures. Another common treatment is a gastrostomy (insertion of a feeding tube) to reduce possible poor nutrition and repeated aspiration pneumonia.

Eye agenesis is a medical condition in which people are born with no eyes.

Caudal regression syndrome or sacral agenesis (or hypoplasia of the sacrum) is a congenital disorder in which there is abnormal fetal development of the lower spine—the caudal partition of the spine.

It occurs at a rate of approximately one per 25,000 live births.

Microlissencephaly is listed in Orphanet database as a rare disease. There is no much information available about the epidemiology of microlissencepahly in literature. A PhD thesis has estimated the prevalence of microlissencepahly in South–Eastern Hungary between July 1992 and June 2006 to be a case every 91,000 live births (0.11:10,000).

Cerebellar agenesis is a rare condition in which a brain develops without the cerebellum. The cerebellum controls smooth movement, and when it does not develop, the rest of the brain must compensate, which it cannot do completely. The condition is not fatal on its own, but people born without a cerebellum experience severe developmental delays, language deficits, and neurological abnormalities. As children with cerebellar agenesis get older, their movements usually improve. It can co-exist with other severe malformations of the central nervous system, like anencephaly, holoprosencephaly, and microencephaly.

The condition was first reported in 1831. 10 cases had been reported as of 1998. Agenesis of one half or another part of the cerebellum is more common than complete agenesis.

Cerebellar agenesis can be caused by mutations in the PTF1A gene.

The condition arises from some factor or set of factors present during approximately the 3rd week to 7th week of fetal development. Formation of the sacrum/lower back and corresponding nervous system is usually nearing completion by the 4th week of development. Due to abnormal gastrulation, the mesoderm migration is disturbed. This disturbance results in symptoms varying from minor lesions of the lower vertebrae to more severe symptoms such as complete fusion of the lower limbs. While the exact cause is unknown, it has been speculated that the condition may be associated with certain dietary deficiencies including a lack or insufficient amounts of folic acid.

Sacral agenesis syndrome (agenesis of the lumbar spine, sacrum, and coccyx, and hypoplasia of the lower extremities) is a well-established congenital anomaly associated with maternal diabetes mellitus (not gestational diabetes). However, other causes are presumably involved, as demonstrated by the rare incidence of caudal regression syndrome (1:60,000) compared to diabetes.

The dominant inherited sacral agenesis (also referred to as Currarino syndrome) is very often correlated with a mutation in the Hb9 (also called HlxB9) gene (shown by Sally Ann Lynch, 1995, Nature Genetics).

It may be the cause of sirenomelia ("Mermaid syndrome").

Cerebellar hypoplasia is characterized by reduced cerebellar volume even though cerebellar shape is (near) normal. It consists of a heterogeneous group of disorder of cerebellar maldevelopment presenting as early onset non progressive ataxia, hypotonia, and motor learning disability. Various causes has been incriminated like hereditary, metabolic, toxic and viral agents. First reported by Crouzon in 1929. In 1940 an unclaimed body came for dissection in London Hospital and was discovered to have no cerebellum. This unique case was appropriately named "human brain without a cerebellum" and was used every year in the Department of Anatomy at Cambridge University in a neuroscience course for medical students.

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

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.

Individuals with CAVD can reproduce with the assistance of modern technology with a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI). However, as the risk of either cystic fibrosis or renal agenesis is likely to be higher in the children, genetic counseling is generally recommended.

Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri). Microlissencephaly is a heterogeneous disorder i.e. it has many different causes and a variable clinical course. Microlissencephaly is a malformation of cortical development (MCD) that occurs due to failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities. Numerous genes have been found to be associated with microlissencephaly, however, the pathophysiology is still not completely understood.

The combination of lissencephaly with severe congenital microcephaly is designated as microlissencephaly only when the cortex is abnormally thick. If such combination exists with a normal cortical thickness (2.5 to 3 mm), it is known as "microcephaly with simplified gyral pattern" (MSGP). Both MLIS and MSGP have a much more severe clinical course than microcephaly alone. They are inherited in autosomal recessive manner. Prior to 2000, the term “microlissencephaly” was used to designate both MLIS and MSGP.

The prevalence rate has been estimated to be less than 1/1,000,000 worldwide. However, it is much more common in the French-Canadian population of the Saguenay and Lac-St-Jean regions of Quebec, Canada, where it has a frequency of about 1 in 2100 in live births, and a carrier rate of 1 in 23.

In 2008 researchers found autosomal dominant mutations in the RET and GDNF genes to be linked to renal agenesis in unrelated stillborn fetuses through PCR and direct sequence analysis . In the study, DNA from 33 stillborn fetuses were sequenced for mutations in RET, GDNF and GFRA1. Nineteen of the fetuses had BRA, ten had URA and 4 had congenital renal dysplasia. Seven of the 19 BRA fetuses were found to have a mutation in the RET gene (37%), while two of the ten URA fetuses did (20%). One of the URA fetuses had two RET mutations and one GDNF mutation. There were no GFRA1 mutations found.

However, the results of Skinner et al. study were questioned by a more recent study with a larger number of cases . In this study 105 fetuses were analyzed. Sixty-five fetuses had BRA while 24 had URA with an abnormal contralateral kidney. Mutations in the RET gene were only found in seven of the fetuses (6.6%).

In 2014 researchers found autosomal recessive mutations in ITGA8 in three members of two unrelated families utilizing Exome Sequencing . One of the families was consanguineous.

In 2017 researchers identified heritable autosomal dominant mutations in the gene GREB1L in two unrelated families as being the cause of both BRA and URA utilizing Exome Sequencing and direct sequencing analysis . This is the first reported genetic lesion implicated in the activation of Retinoic Acid Receptor (RAR) Targets that has been associated with renal agenesis in humans. The researchers found two different GREB1L mutations, each being unique to their respective pedigrees. In total, there were 23 individuals analyzed between the two families, four of which had BRA and five of which had URA. GREB1L mutations were identified in all of the affected individuals as well as in three unaffected family members, demonstrating incomplete penetrance and variable expressivity.

There are several hundred to perhaps several thousand genes that, if they had the right kind of mutation, could lead to renal agenesis in humans. It is possible that each individual or family experiencing renal agenesis has a unique gene or genetic mutation causing the condition due to the fact that there are so many genes that are critical to proper renal development. See Rosenblum S et al. for an excellent review of Congenital abnormalities of the Kidney and Urinary Tract

Chromosomal anomalies have been associated with BRA in certain cases (chromosomes 1, 2, 5 and 21), but these anomalies were not inherited and have not been observed in subsequent cases. Additionally, neither extreme substance abuse or environmental factors (high power line, mercury, ground water issues, etc.) have been reported to be linked to an increased incidence of BRA or other cause of Potter sequence. However, renal agenesis and other causes of oligohydramnios sequence have been linked to a number of other conditions and syndromes to include Down syndrome, Kallmann syndrome, branchio-oto-renal syndrome and others.

The cause of arrhinia is not known. Akkuzu's study of the literature found that all cases had presented a normal antenatal history.

There are two main populations of CAVD; the larger group is associated with

cystic fibrosis and occurs because of a mutation in the CFTR gene, while the smaller group (estimated between 10 and 40%) is associated with Unilateral Renal agenesis (URA). The genetic basis of this second group is not well understood.

Mutation of the CFTR gene is found to result in obstructive azoospermia in postpubertal males with cystic fibrosis. Strikingly, CAVD is one of the most consistent features of cystic fibrosis as it affects 98-99% of individuals in this CF patient population. In contrast, acute or persistent respiratory symptoms present in only 51% of total CF patients.

In the subset of males with both CBAVD and URA, the CFTR mutation has been shown to occur at a rate only slightly higher than the overall population. Thus, McCallum, et al. have suggested another mutation may be responsible for this condition.