Neurodevelopmental disorders

A neurodevelopmental disorder, or disorder of neural development, is an impairment of the growth and development of the brain or central nervous system. One narrower use of the term refers to a disorder of brain function which affects emotion, learning ability and memory and which unfolds as the individual grows. The term is sometimes erroneously used as an exclusive synonym for autism and autism spectrum disorders.

Disorders considered to be neurodevelopmental in origin or to have neurodevelopmental consequences when they occur in infancy and childhood includes attention deficit hyperactivity disorder (ADHD), autism and autism spectrum disorders, traumatic brain injury (including congenital injuries such as those which cause cerebral palsy ), communication, speech and language disorders, genetic disorders such as fragile-X syndrome, Down syndrome and Rett syndrome, epilepsy, fetal alcohol syndrome, learning disorders, neurological and psychiatric disorders. Neurodevelopmental disorders are associated with widely varying degrees of mental, emotional, physical and economic burden to individuals, families and society in general.

Causes
Causes include deprivation, genetic and metabolic diseases, immune disorders, infectious diseases, nutritional factors, physical trauma, toxic and environmental factors.

Some neurodevelopmental disorders such as autism and other pervasive developmental disorders are considered to be multifactoral syndromes (with many causes but more specific neurodevelopmental manifestation). However other multifactoral syndromes such as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections PANDAS are presently thought to have a more specific primary causation as well as a specific neurodevelopmental manifestation.

Deprivation
Infants and children require loving emotional nurture from caregivers—there is a spectrum of problems arising from the lack of it. The most severe deprivation disorder, hospitalism, was described in 1897 as a wasting away to the point of death. A sublethal form, anaclitic depression was first described by René Spitz in the 1940s. It occurred in infants over the age of six months who suffered the loss of their mothers, who then became depressed and show behavioral retardation (delay in reaching developmental milestones, especially as relate to social behaviors). Behavioral retardation, as in the reactive attachment disorders, has been observed in emotionally deprived children living with their families. 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 have risk of poor developmental outcomes which, left untreated, may lead to severe, autistic-like behaviors. Despite its biologic basis, caregivers can ameliorate blindness-related sensory deprivation. This can lead to positive neurodevelopmental outcome, as in the cases of author Helen Keller who was trained in the use of tactile sign language, and musicians such as Arthel "Doc" Watson and Ray Charles who remained emotionally connected to others via their sense of hearing.

Genetic disorders
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).

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 defect". Rett syndrome, another X-linked disorder, produces severe functional limitations. Williams syndrome is caused by small deletions of genetic material from chromosome 7.

Immune dysfunction
Immune reactions during pregnancy, both maternal and of the developing child can produce neurodevelopmental disorders. One typical immune reaction in infants and children is PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection produce abnormal movements of the body, emotional disturbance and obsessive compulsive disorder symptoms. 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 which 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.)

Infectious diseases
There are a number of infectious diseases which can be transmitted either congenitally or in early childhood and which can cause serious neurodevelopmental disorders such as schizophrenia. 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 multifactoral disorder) and phenylketonuria (an inborn error of metabolism). There are many such inherited diseases which may directly affect the child's metabolism and neural development but less commonly they can indirectly affect the child during gestation. (See also teratology).

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

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. However usually the neurodevelopmental symptoms decrease in later childhood.

Phenylketonuria, also known as PKU is an inborn error of metabolism which can induce neurodevelopmental disorders in the child. 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.

Nutrition
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. (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 multifactoral causes.) Another deficiency, iodine deficiency, produces a spectrum of neurodevelopmental disorders from mild emotional disturbance to severe mental retardation.

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. It has been discovered that iron supplementation in baby formula is linked to lowered I.Q. and other neurodevelopmental delays.

Trauma
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) of neurodevelopmental syndromes. It may be subdivided into two major categories, congenital injury (including injury resulting from otherwise uncomplicated premature birth) 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.

Overwhelmingly, in industrial nations the most common causes of childhood brain trauma are falls and transportation-related incidents. Child maltreatement such as shaken baby syndrome can produce neurodevelopmental consequences including blindness, neuromotor deficits and cognitive impairment. According to information published by the American Association of Neurological Surgeons, Sports injuries account for 21% of the US incidence, however their site includes transportation-related sports injuries. They assert that cycling produced 64,993 head injuries requiring emergency room visits in 2007 while the second most common cause, football, only produced 36,412.

Toxic and environmental factors
One well known environmental toxic cause of neurodevelopmental disorders is heavy metal poisoning, with a prominent 20th century example being Minamata disease. Developmental mercury poisoning can cause a spectrum of problems from mild impairment of emotional development to the full blown syndrome of peripheral nerve damage, visual impairment, impaired coordination and ambulation, hallucinations, mental retardation, depression and death. However other metals such as lead, manganese, arsenic, cadmium and iron, as well as pesticides, tobacco and other environmental toxins are also implicated as causative factors.