Neurodevelopmental disorder

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Neurodevelopmental disorders[1] are impairments of the growth and development of the brain or central nervous system. A narrower use of the term refers to a disorder of brain function that affects emotion, learning ability, self-control and memory and that unfolds as the individual grows. The term is sometimes erroneously used as an exclusive synonym for autism and autism spectrum disorders.

Disorders considered neurodevelopmental in origin, or that have neurodevelopmental consequences when they occur in infancy and childhood, include:

Neurodevelopmental disorders are associated with widely varying degrees of difficulty which may have significant mental, emotional, physical, and economic consequences for individuals, and in turn their families and society in general.


The development of the brain is orchestrated, tightly regulated, and genetically encoded process with clear influence from the environment. This suggests that any deviation from this program early in life can result in neurodevelopmental disorders and, depending on specific timing, might lead to distinct pathology later in life. [5] Because of that, there are many causes of neurodevelopmental disorder, which can range from deprivation, genetic and metabolic diseases, immune disorders, infectious diseases, nutritional factors, physical trauma, and toxic and environmental factors.

Some neurodevelopmental disorders—such as autism and other pervasive developmental disorders—are considered multifactorial syndromes (with many causes but more specific neurodevelopmental manifestation).[6]


Behavioral retardation, as in the reactive attachment disorders, has been observed in emotionally deprived children living with their families.[7][8] However, prominent modern thought attributes other causative mechanisms to autism and autistic spectrum disorders. (see Autism)

However, nurture is not the only cause of deprivation that leads to neurodevelopmental sequellae. A common example of sensory deprivation due to biologic factors is blindness. Blind infants are at risk for poor developmental outcomes that if left untreated can lead to severe, autistic-like behaviors.[9] Despite its biologic basis, caregivers can ameliorate blindness-related sensory deprivation.[10] This can lead to positive neurodevelopmental outcome, as in the cases of author Helen Keller,[11] who was trained in the use of tactile sign language, and musicians such as Arthel "Doc" Watson[12] and Ray Charles who remained emotionally connected to others via their sense of hearing.

Genetic disorders

A child with Down syndrome

A prominent example of a genetically determined neurodevelopmental disorder is Trisomy 21, also known as Down syndrome. This disorder usually results from an extra chromosome 21, although in uncommon instances it is related to other chromosomal abnormalities such as translocation of the genetic material. It is characterized by short stature, epicanthal (eyelid) folds, abnormal fingerprints, and palm prints, heart defects, poor muscle tone (delay of neurological development) and mental retardation (delay of intellectual development).[3]

Less commonly known genetically determined neurodevelopmental disorders include Fragile X syndrome, Rett syndrome, and Williams syndrome. Fragile X syndrome was first described in 1943 by J.P. Martin and J. Bell, studying persons with family history of sex-linked "mental defects".[13] Rett syndrome, another X-linked disorder, produces severe functional limitations.[14] Williams syndrome is caused by small deletions of genetic material from chromosome 7.[15]

Immune dysfunction

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,[16] or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection.[17] 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,[18] so sometimes several family members may suffer from one or both of them following an epidemic of Strep infection.

Infectious diseases

A number of infectious diseases can be transmitted either congenitally or in early childhood, and can cause serious neurodevelopmental disorders, such as schizophrenia.[19] Congenital toxoplasmosis may result in formation of cysts in the brain and other organs, causing a variety of neurological deficits. Congenital syphilis may progress to neurosyphilis if it remains untreated. Measles can progress to subacute sclerosing panencephalitis. Congenital rubella syndrome can produce schizophrenia in addition to multiple other symptoms.

Metabolic disorders

Metabolic disorders, present in either the mother or the child, can cause neurodevelopmental disorders. Two examples are diabetes mellitus (a multifactorial disorder) and phenylketonuria (an inborn error of metabolism). Many such inherited diseases may directly affect the child's metabolism and neural development[20] but less commonly they can indirectly affect the child during gestation. (See also teratology).

In a child, type 1 diabetes can produce neurodevelopmental damage by the effects of excess or insufficient glucose. The problems continue and may worsen throughout childhood if the diabetes is not well controlled.[21] Type 2 diabetes may be preceded in its onset by impaired cognitive functioning.[22]

However a non-diabetic fetus can also be subjected to glucose effects if its mother has undetected gestational diabetes. Maternal diabetes causes excessive birth size, making it harder for the infant to pass through the birth canal without injury or it can directly produce early neurodevelopmental deficits. Usually the neurodevelopmental symptoms will decrease in later childhood.[23]

Phenylketonuria, also known as PKU, is an inborn error of metabolism that can induce neurodevelopmental disorders in children. Children with PKU require a strict diet to prevent mental retardation and other disorders. In the maternal form of PKU, excessive maternal phenylalanine can be absorbed by the fetus even if the fetus has not inherited the disease. This can produce mental retardation and other disorders.[24][25]


Nutritional deficits may cause neurodevelopmental disorders, such as spina bifida, which is common, and anencephaly, which is rare. Both disorders are neural tube defects with malformation and dysfunction of the nervous system and its supporting structures, leading to serious physical disability as well as its emotional sequellae. The most common nutritional cause of neural tube defects is maternal deficiency of folic acid, a B vitamin usually found in fruits, vegetables, whole grains, and milk products.[26][27] (Neural tube defects are also caused by medications and other environmental causes, many of which interfere with folate metabolism, thus they are considered to have multifactorial causes.)[28][29] Another deficiency, iodine deficiency, produces a spectrum of neurodevelopmental disorders ranging from mild emotional disturbance to severe mental retardation. (see also cretinism)

Excesses in both maternal and infant diets may cause disorders as well, with foods or food supplements proving toxic in large amounts. For instance in 1973 K.L. Jones and D.W. Smith of the University of Washington Medical School in Seattle found a pattern of "craniofacial, limb, and cardiovascular defects associated with prenatal onset growth deficiency and developmental delay" in children of alcoholic mothers. This disorder, now called fetal alcohol syndrome, has significant symptom overlap with several other entirely unrelated neurodevelopmental disorders.[30] It has been discovered that iron supplementation in baby formula is linked to lowered I.Q. and other neurodevelopmental delays.[31]


CT scan showing epidural hematoma, a type of traumatic brain injury (upper left)

Brain trauma in the developing human is a common cause (over 400,000 injuries per year in the US alone, without clear information as to how many produce developmental sequellae)[32] of neurodevelopmental syndromes. It may be subdivided into two major categories, congenital injury (including injury resulting from otherwise uncomplicated premature birth)[2] and injury occurring in infancy or childhood. Common causes of congenital injury are asphyxia (obstruction of the trachea), hypoxia (lack of oxygen to the brain) and the mechanical trauma of the birth process itself.

See also



  • Tager-Flusberg, Helen (1999). Neurodevelopmental disorders. Cambridge, Mass: MIT Press. ISBN 0-262-20116-X.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  • Brooks, David R.; Walter Wolfgang Fleischhacker (2006). Neurodevelopmental Disorders. Berlin: Springer. ISBN 3-211-26291-1.CS1 maint: multiple names: authors list (link)<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>


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  2. 2.0 2.1 Murray RM, Lewis SW (September 1987). "Is schizophrenia a neurodevelopmental disorder?". Br Med J (Clin Res Ed). 295 (6600): 681–2. doi:10.1136/bmj.295.6600.681. PMC 1247717. PMID 3117295.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  3. 3.0 3.1 Facts about down syndrome
  4. 4.0 4.1 Bolvin, MJ; Kakooza, AM; Warf, BC; Davidson, LL; Grigorenko, EL (November 2015). "Reducing neurodevelopmental disorders and disability through research and interventions". Nature. 527 (7578): S155-60. doi:10.1038/nature16029. PMID 26580321.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  5. Pletikos, Mihovil (22 January 2014). "Temporal Specification and Bilaterality of Human Neocortical Topographic Gene Expression". Neuron. 81 (2): 321–332. doi:10.1016/j.neuron.2013.11.018.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. Samaco RC, Hogart A, LaSalle JM (February 2005). "Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3". Hum. Mol. Genet. 14 (4): 483–92. doi:10.1093/hmg/ddi045. PMC 1224722. PMID 15615769.CS1 maint: multiple names: authors list (link)<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  11. Keller, Helen (2002). The story of my life (100th Anniversary Edition) (Signet Classics (Paperback)). Signet Classics. ISBN 0-451-52825-5.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  12. Miller, Dan (October 2–8, 2000). "Doc Watson: flatpicking legend". Featured Artist. Flatpicking Guitar Magazine. Retrieved 2008-08-17.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  14. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (October 1999). "Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2". Nat. Genet. 23 (2): 185–8. doi:10.1038/13810. PMID 10508514.CS1 maint: multiple names: authors list (link)<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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