Immune reactions during pregnancy, both maternal and of the developing child, may produce neurodevelopmental disorders. One typical immune reaction in infants and children is PANDAS, or "Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection". Another disorder is Sydenham's chorea, which results in more abnormal movements of the body and fewer psychological sequellae. Both are immune reactions against brain tissue that follow infection by "Streptococcus" bacteria. Susceptibility to these immune diseases may be genetically determined, so sometimes several family members may suffer from one or both of them following an epidemic of Strep infection.

Systemic infections can result in neurodevelopmental consequences, when they occur in infancy and childhood of humans, but would not be called a primary neurodevelopmental disorder per se, as for example HIV Infections of the head and brain, like brain abscesses, meningitis or encephalitis have a high risk of causing neurodevelopmental problems and eventually a disorder. For example, measles can progress to subacute sclerosing panencephalitis.

A number of infectious diseases can be transmitted either congenitally (before or at birth), and can cause serious neurodevelopmental problems, as for example the viruses HSV, CMV, rubella (congenital rubella syndrome), Zika virus, or bacteria like "Treponema pallidum" in congenital syphilis, which may progress to neurosyphilis if it remains untreated. Protozoa like "Plasmodium" or "Toxoplasma" which can cause congenital toxoplasmosis with multiple cysts in the brain and other organs, leading to a variety of neurological deficits.

Some cases of schizophrenia may be related to congenital infections though the majority are of unknown causes.

Autism spectrum disorders tend to be highly comorbid with other disorders. Comorbidity may increase with age and may worsen the course of youth with ASDs and make intervention/treatment more difficult. Distinguishing between ASDs and other diagnoses can be challenging, because the traits of ASDs often overlap with symptoms of other disorders, and the characteristics of ASDs make traditional diagnostic procedures difficult.

The most common medical condition occurring in individuals with autism spectrum disorders is seizure disorder or epilepsy, which occurs in 11-39% of individuals with ASD. Tuberous sclerosis, a medical condition in which non-malignant tumors grow in the brain and on other vital organs, occurs in 1-4% of individuals with ASDs.

Intellectual disabilities are some of the most common comorbid disorders with ASDs. Recent estimates suggest that 40-69% of individuals with ASD have some degree of an intellectual disability, more likely to be severe for females. A number of genetic syndromes causing intellectual disability may also be comorbid with ASD, including fragile X syndrome, Down syndrome, Prader-Willi and Angelman syndromes, and Williams syndrome.

Learning disabilities are also highly comorbid in individuals with an ASD. Approximately 25-75% of individuals with an ASD also have some degree of a learning disability.

Various anxiety disorders tend to co-occur with autism spectrum disorders, with overall comorbidity rates of 7-84%. Rates of comorbid depression in individuals with an ASD range from 4–58%. The relationship between ASD and schizophrenia remains a controversial subject under continued investigation, and recent meta-analyses have examined genetic, environmental, infectious, and immune risk factors that may be shared between the two conditions.

Deficits in ASD are often linked to behavior problems, such as difficulties following directions, being cooperative, and doing things on other people's terms. Symptoms similar to those of attention deficit hyperactivity disorder (ADHD) can be part of an ASD diagnosis.

Sensory processing disorder is also comorbid with ASD, with comorbidity rates of 42–88%.

Several prenatal and perinatal complications have been reported as possible risk factors for autism. These risk factors include maternal gestational diabetes, maternal and paternal age over 30, bleeding after first trimester, use of prescription medication (e.g. valproate) during pregnancy, and meconium in the amniotic fluid. While research is not conclusive on the relation of these factors to autism, each of these factors has been identified more frequently in autistic children compared to their non-autistic siblings and other normally developing youth.

Low vitamin D levels in early development has been hypothesized as a risk factor for autism.

Among children, the cause of intellectual disability is unknown for one-third to one-half of cases. About 5% of cases are inherited from a person's parents. Genetic defects that cause intellectual disability but are not inherited can be caused by accidents or mutations in genetic development. Examples of such accidents are development of an extra chromosome 18 (trisomy 18) and Down syndrome, which is the most common genetic cause. Velocariofacial syndrome and fetal alcohol spectrum disorders are the two next most common causes. However, doctors have found many other causes. The most common are:

- Genetic conditions. Sometimes disability is caused by abnormal genes inherited from parents, errors when genes combine, or other reasons. The most prevalent genetic conditions include Down syndrome, Klinefelter syndrome, Fragile X syndrome (common among boys), neurofibromatosis, congenital hypothyroidism, Williams syndrome, phenylketonuria (PKU), and Prader–Willi syndrome. Other genetic conditions include Phelan-McDermid syndrome (22q13del), Mowat–Wilson syndrome, genetic ciliopathy, and Siderius type X-linked intellectual disability () as caused by mutations in the "PHF8" gene (). In the rarest of cases, abnormalities with the X or Y chromosome may also cause disability. 48, XXXX and 49, XXXXX syndrome affect a small number of girls worldwide, while boys may be affected by 49, XXXXY, or 49, XYYYY. 47, XYY is not associated with significantly lowered IQ though affected individuals may have slightly lower IQs than non-affected siblings on average.

- Problems during pregnancy. Intellectual disability can result when the fetus does not develop properly. For example, there may be a problem with the way the fetus' cells divide as it grows. A pregnant person who drinks alcohol (see fetal alcohol spectrum disorder) or gets an infection like rubella during pregnancy may also have a baby with intellectual disability.

- Problems at birth. If a baby has problems during labor and birth, such as not getting enough oxygen, he or she may have developmental disability due to brain damage.

- Exposure to certain types of disease or toxins. Diseases like whooping cough, measles, or meningitis can cause intellectual disability if medical care is delayed or inadequate. Exposure to poisons like lead or mercury may also affect mental ability.

- Iodine deficiency, affecting approximately 2 billion people worldwide, is the leading preventable cause of intellectual disability in areas of the developing world where iodine deficiency is endemic. Iodine deficiency also causes goiter, an enlargement of the thyroid gland. More common than full-fledged cretinism, as intellectual disability caused by severe iodine deficiency is called, is mild impairment of intelligence. Certain areas of the world due to natural deficiency and governmental inaction are severely affected. India is the most outstanding, with 500 million suffering from deficiency, 54 million from goiter, and 2 million from cretinism. Among other nations affected by iodine deficiency, China and Kazakhstan have instituted widespread iodization programs, whereas, as of 2006, Russia had not.

- Malnutrition is a common cause of reduced intelligence in parts of the world affected by famine, such as Ethiopia.

- Absence of the arcuate fasciculus.

The syndrome primarily affects young males. Preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of those affected do not live beyond 25 years of age, with deaths attributed to the impaired immune function.

Intellectual disability affects about 2–3% of the general population. 75–90% of the affected people have mild intellectual disability. Non-syndromic or idiopathic ID accounts for 30–50% of cases. About a quarter of cases are caused by a genetic disorder. Cases of unknown cause affect about 95 million people as of 2013.

Intellectual disability in children can be caused by genetic or environmental factors. The individual could have a natural brain malformation or pre or postnatal damage done to the brain caused by drowning or a traumatic brain injury, for example. Nearly 30 to 50% of individuals with intellectual disability will never know the cause of their diagnosis even after thorough investigation.

Prenatal causes of intellectual disability include:

- Congenital infections such as cytomegalovirus, toxoplasmosis, herpes, syphilis, rubella and human immunodeficiency virus

- Prolonged maternal fever in the first trimester

- Exposure to anticonvulsants or alcohol

- Untreated maternal phenylketonuria (PKU)

- Complications of prematurity, especially in extremely low-birth-weight infants

- Postnatal exposure to lead

Single-gene disorders that result in intellectual disability include:

- Fragile X syndrome

- Neurofibromatosis

- Tuberous sclerosis

- Noonan's syndrome

- Cornelia de Lange's syndrome

These single-gene disorders are usually associated with atypical physical characteristics.

About 1/4 of individuals with intellectual disability have a detectable chromosomal abnormality. Others may have small amounts of deletion or duplication of chromosomes, which may go unnoticed and therefore, undetermined.

Isolated

1. Familial (autosomal recessive) microcephaly

2. Autosomal dominant microcephaly

3. X-linked microcephaly

4. Chromosomal (balanced rearrangements and ring chromosome)

Syndromes

- Chromosomal

1. Poland syndrome

2. Down syndrome

3. Edward syndrome

4. Patau syndrome

5. Unbalanced rearrangements

- Contiguous gene deletion

1. 4p deletion (Wolf–Hirschhorn syndrome)

2. 5p deletion (Cri-du-chat)

3. 7q11.23 deletion (Williams syndrome)

4. 22q11 deletion (DiGeorge syndrome)

- Single gene defects

1. Smith–Lemli–Opitz syndrome

2. Seckel syndrome

3. Cornelia de Lange syndrome

4. Holoprosencephaly

5. Primary microcephaly 4

6. Wiedemann-Steiner syndrome

Acquired

- Disruptive injuries

1. Ischemic stroke

2. Hemorrhagic stroke

3. Death of a monozygotic twin

- Vertically transmitted infections

1. Congenital cytomegalovirus infection

2. Toxoplasmosis

3. Congenital rubella syndrome

4. Zika virus

- Drugs

1. Fetal hydantoin syndrome

2. Fetal alcohol syndrome

Other

1. Radiation exposure to mother

2. Maternal malnutrition

3. Maternal phenylketonuria

4. Poorly controlled gestational diabetes

5. Hyperthermia

6. Maternal hypothyroidism

7. Placental insufficiency

Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. There is usually a more specific condition which causes this delay, such as Fragile X syndrome or other chromosonal abnormalities. However, it is sometimes difficult to identify this underlying condition.

Other terms associated with this condition are failure to thrive (which focuses on lack of weight gain and physical development), intellectual disability (which focuses on intellectual deficits and the changes they cause to development) and developmental disability (which can refer to both intellectual and physical disability altering development).

A 2013 review stated that life expectancy for FXS was 12 years lower than the general population and that the causes of death were similar to those found for the general population.

Lujan–Fryns syndrome is a rare X-linked dominant syndrome, and is therefore more common in males than females. Its prevalence within the general population has not yet been determined.

Several X-linked syndromes include intellectual disability as part of the presentation. These include:

- Coffin–Lowry syndrome

- MASA syndrome

- MECP2 duplication syndrome

- X-linked alpha thalassemia mental retardation syndrome

- mental retardation and microcephaly with pontine and cerebellar hypoplasia

X-linked intellectual disability (previously known as X-linked mental retardation) refers to forms of intellectual disability which are specifically associated with X-linked recessive inheritance.

As with most X-linked disorders, males are more heavily affected than females. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.

Unlike many other types of intellectual disability, the genetics of these conditions are relatively well understood. It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified.

X-linked intellectual disability accounts for ~16% of all cases of intellectual disability in males.

Micro syndrome also known as WARBM, and Warburg–Sjo–Fledelius syndrome, is a rare autosomal recessive genetic disorder characterized by microcephaly, microcornea, congenital cataract, intellectual or developmental disability, optic atrophy, and hypogenitalism.

Alopecia contractures dwarfism mental retardation syndrome or (ACD mental retardation syndrome) is a developmental disorder which causes mainly baldness and dwarfism in combination with intellectual disability; skeletal anomalies, caries and nearsightedness are also typical.

The ACD mental retardation syndrome was first described in 1980 by Albert Schinzel and only few cases have since been identified in the world. At the time Dr. Schinzel made no conclusion of the hereditary pattern of this syndrome but similarities between cases reported by year 2000 seem to suggest autosomal or x-linked recessive inheritance or possibly a dominant mutation caused by mosaicism as causes of this syndrome.

There is no specific treatment for micro syndrome, but there are ways to help the disorders, and illnesses that come with it. Many individuals with Micro Syndrome need permanent assistance from their disorders and inabilities to move and support themselves. Seizures are not uncommon and patients should get therapy to help control them, and many patients also require wheelchairs to move, so an assistant would be needed at all times.

Those with micro syndrome are born appearing normal. At the age of one, mental and physical delays become apparent, along with some limb spasms. By the age of eight micro syndrome has already set in, and the patient will have joint contractures, Ocular Atrophy will become noticeable, the patient will most likely lose ability to walk, speak, and sometimes move at all.

As the syndrome is due to a chromosomal non-disjunction event, the recurrence risk is not high compared to the general population. There has been no evidence found that indicates non-disjunction occurs more often in a particular family.

Genetic

- Inborn errors of metabolism

1. Congenital disorder of glycosylation

2. Mitochondrial disorders

3. Peroxisomal disorder

4. Glucose transporter defect

5. Menkes disease

6. Congenital disorders of amino acid metabolism

7. Organic acidemia

Syndromes

- Contiguous gene deletion

1. 17p13.3 deletion (Miller–Dieker syndrome)

- Single gene defects

1. Rett syndrome (primarily girls)

2. Nijmegen breakage syndrome

3. X-linked lissencephaly with abnormal genitalia

4. Aicardi–Goutières syndrome

5. Ataxia telangiectasia

6. Cohen syndrome

7. Cockayne syndrome

Acquired

- Disruptive injuries

1. Traumatic brain injury

2. Hypoxic-ischemic encephalopathy

3. Ischemic stroke

4. Hemorrhagic stroke

- Infections

1. Congenital HIV encephalopathy

2. Meningitis

3. Encephalitis

- Toxins

1. Lead poisoning

2. Chronic renal failure

- Deprivation

1. Hypothyroidism

2. Anemia

3. Congenital heart disease

4. Malnutrition

Genetic factors may play a role in causing some cases of microcephaly. Relationships have been found between autism, duplications of chromosomes, and macrocephaly on one side. On the other side, a relationship has been found between schizophrenia, deletions of chromosomes, and microcephaly. Moreover, an association has been established between common genetic variants within known microcephaly genes ("MCPH1, CDK5RAP2") and normal variation in brain structure as measured with magnetic resonance imaging (MRI)i.e., primarily brain cortical surface area and total brain volume.

The spread of Aedes mosquito-borne Zika virus has been implicated in increasing levels of congenital microcephaly by the International Society for Infectious Diseases and the US Centers for Disease Control and Prevention. Zika can spread from a pregnant woman to her fetus. This can result in other severe brain malformations and birth defects. A study published in The New England Journal of Medicine has documented a case in which they found evidence of the Zika virus in the brain of a fetus that displayed the morphology of microcephaly.

Opitz G/BBB Syndrome is a rare genetic condition caused by one of two major types of mutations: MID1 mutation on the short (p) arm of the X chromosome or a mutation of the 22q11.2 gene on the 22nd chromosome. Since it is a genetic disease, it is an inherited condition. However, there is an extremely wide variability in how the disease presents itself.

In terms of prevention, several researchers strongly suggest prenatal testing for at-risk pregnancies if a MID1 mutation has been identified in a family member. Doctors can perform a fetal sex test through chromosome analysis and then screen the DNA for any mutations causing the disease. Knowing that a child may be born with Opitz G/BBB syndrome could help physicians prepare for the child’s needs and the family prepare emotionally. Furthermore, genetic counseling for young adults that are affected, are carriers or are at risk of carrying is strongly suggested, as well (Meroni, Opitz G/BBB syndrome, 2012). Current research suggests that the cause is genetic and no known environmental risk factors have been documented. The only education for prevention suggested is genetic testing for at-risk young adults when a mutation is found or suspected in a family member.

The vast majority of cases are due to spontaneous genetic mutations.

It can be associated with mutations affecting the cohesin complex.

Multiple genes have been associated with the condition. In 2004, researchers at the Children's Hospital of Philadelphia (United States) and the University of Newcastle upon Tyne (England) identified a gene (NIPBL) on chromosome 5 that causes CdLS when it is mutated. Since then, additional genes have been found (SMC1A, SMC3 and HDAC8) that cause CdLS when changed. There are likely other genes as well. Researchers hope to gain a better understanding of why CdLS varies so widely from one individual to another and what can be done to improve the quality of life for people with the syndrome.

The latter two genes seem to correlate with a milder form of the syndrome.

In July 2012, the fourth “CdLS gene”—HDAC8—was announced. Many parents and professionals have

questions about this latest finding and what it means. HDAC8 is an X-linked gene, meaning it is located on the X chromosome. Individuals with CdLS who have the gene change in HDAC8 make up just a small portion of all people with CdLS.

Evidence of a linkage at chromosome 3q26.3 is mixed.

1p36 deletion syndrome (also known as monosomy 1p36) is a congenital genetic disorder characterized by moderate to severe intellectual disability, delayed growth, hypotonia, seizures, limited speech ability, malformations, hearing and vision impairment, and distinct facial features. The symptoms may vary, depending on the exact location of the chromosomal deletion.

The condition is caused by a genetic deletion (loss of a segment of DNA) on the outermost band on the short arm (p) of chromosome 1. It is one of the most common deletion syndromes. It is estimated that the syndrome occurs in one in every 5,000 to 10,000 births. Knowledge of the disorder has increased a great deal over the last decade, mainly because more patients have been accurately diagnosed and described in international medical literature.

The collecting system is the structure that collects urine directly from the kidney tissue and routes it by way of the ureter to the bladder. Structural renal abnormalities are rare in both sexes.

Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH), also known as Mental retardation, X-linked, syndromic, Najm type (MRXSNA), is a rare genetic disorder of infants characterised by intellectual disability and pontocerebellar hypoplasia.

The disorder is associated with a mutation in the "CASK" gene which is transmitted in an X-linked manner. As with the vast majority of genetic disorders, there is no known cure to MICPCH.

The following values seem to be aberrant in children with CASK gene defects: lactate, pyruvate, 2-ketoglutarate, adipic acid and suberic acid, which seems to backup the proposal that CASK affects mitochondrial function. It is also speculated that phosphoinositide 3-kinase in the inositol metabolism is impacted in the disease, causing folic acid metabolization problems.

M2DS is one of the several types of X-linked intellectual disability. The cause of M2DS is a duplication of the MECP2 or Methyl CpG binding protein 2 gene located on the X chromosome (Xq28). The MeCP2 protein plays a pivotal role in regulating brain function. Increased levels of MECP2 protein results in abnormal neural function and impaired immune system. Mutations in the MECP2 gene are also commonly associated with Rett syndrome in females. Advances in genetic testing and more widespread use of Array Comparative Genomic Hybridization has led to increased diagnosis of MECP2 duplication syndrome. It is thought to represent ~1% of X-linked male mental disability cases.