Neurodevelopmental disorder

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Neurodevelopmental disorder
Specialty Psychiatry, neurology

Neurodevelopmental disorders are a group of conditions that begin to emerge during childhood (or the development of the nervous system). According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) published in 2013, these conditions generally appear in early childhood, usually before children start school, and can persist into adulthood. [1] The key characteristic of all these disorders is that they negatively impact a person's functioning in one or more domains of life (personal, social, academic, occupational) depending on the disorder and deficits it has caused. All of these disorders and their levels of impairment exist on a spectrum, and affected individuals can experience varying degrees of symptoms and deficits, despite having the same diagnosis. [1] [2]

Contents

The DSM-5 classifies neurodevelopmental disorders into six overarching groups.

  1. Intellectual disability (intellectual development disorder)
  2. Communication disorders
  3. Autism spectrum disorder (ASD)
  4. Attention-deficit/hyperactivity disorder (ADHD)
  5. Neurodevelopmental motor disorders
  6. Specific learning disorders

These disorders are commonly comorbid conditions, meaning that a person affected by one of these disorders will usually meet criteria for a second disorder. [1] [2]

Classification

Intellectual disability (intellectual development disorder)

Intellectual disabilities (IDs), or intellectual development disorder, are defined by the DSM-5 as "deficits in general mental abilities". [1] They affect a person's ability to process information, learn or retain information, think critically or abstractly, and solve problems. They ultimately inhibit a person's ability to adapt to their surroundings, to the extent that individuals may fail to meet milestones of independent functioning or social responsibility in one or more activities of daily living. [1] Global developmental delay (GDD) is categorized under intellectual disability and "is diagnosed when an individual fails to meet expected developmental milestones in several areas of intellectual functioning." [1]

Communication disorders

Communication disorder

Autism spectrum disorder (ASD)

Autism spectrum disorder (ASD)

Attention-deficit/hyperactivity disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD)

Neurodevelopmental motor disorders

Motor disorders including developmental coordination disorder, stereotypic movement disorder, and tic disorders (such as Tourette's syndrome), and CAS - Apraxia of speech

Specific learning disorders

Specific learning disorders

Currently being researched

There are neurodevelopmental research projects examining potential new classifications of disorders including:

  1. Nonverbal learning disorder (NLD or NVLD), a neurodevelopmental disorder thought to be linked to white matter in the right hemisphere of the brain and generally considered to include (a) low visuospatial intelligence; (b) discrepancy between verbal and visuospatial intelligence; (c) visuoconstructive and fine-motor coordination skills; (d) visuospatial memory tasks; (e) reading better than mathematical achievement; and (f) socioemotional skills. [3] [4] [5] While Nonverbal learning disorder is not categorized in the ICD or DSM as an discrete classification, "the majority of researchers and clinicians agree that the profile of NLD clearly exists (but see Spreen, 2011, for an exception [6] ), but they disagree on the need for a specific clinical category and on the criteria for its identification." [7]

Presentation

Consequences

The multitude of neurodevelopmental disorders span a wide range of associated symptoms and severity, resulting in different degrees of mental, emotional, physical, and economic consequences for individuals, and in turn families, social groups, and society. [8]

Causes

The development of the nervous system is tightly regulated and timed; it is influenced by both genetic programs and the prenatal environment. Any significant deviation from the normal developmental trajectory early in life can result in missing or abnormal neuronal architecture or connectivity. [9] Because of the temporal and spatial complexity of the developmental trajectory, there are many potential causes of neurodevelopmental disorders that may affect different areas of the nervous system at different times and ages. These range from social deprivation, genetic and metabolic diseases, immune disorders, infectious diseases, nutritional factors, physical trauma, and toxic and prenatal environmental factors. Some neurodevelopmental disorders, such as autism and other pervasive developmental disorders, are considered multifactorial syndromes which have many causes that converge to a more specific neurodevelopmental manifestation. [10]

Social deprivation

Deprivation from social and emotional care causes severe delays in brain and cognitive development. [11] Studies with children growing up in Romanian orphanages during Nicolae Ceauşescu's regime reveal profound effects of social deprivation and language deprivation on the developing brain. These effects are time-dependent. The longer children stayed in negligent institutional care, the greater the consequences. By contrast, adoption at an early age mitigated some of the effects of earlier institutionalization (abnormal psychology). [12]

Genetic disorders

A child with Down syndrome Child piggyback2.jpg
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, [13] 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 intellectual disabilities (delay of intellectual development). [14]

Less commonly known genetically determined neurodevelopmental disorders include Fragile X syndrome. Fragile X syndrome was first described in 1943 by Martin and Bell, studying persons with family history of sex-linked "mental defects". [15] Rett syndrome, another X-linked disorder, produces severe functional limitations. [16] Williams syndrome is caused by small deletions of genetic material from chromosome 7. [17] The most common recurrent Copy Number Variant disorder is 22q11.2 deletion syndrome (formerly DiGeorge or velocardiofacial syndrome), followed by Prader-Willi syndrome and Angelman syndrome. [18]

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, [19] or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection. [20] 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, [21] so sometimes several family members may have one or both of them following an epidemic of Strep infection.[ citation needed ]

Infectious diseases

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. For example HIV [22] 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 congenitally (either 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 [22] 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. [23]

Metabolic disorders

Metabolic disorders 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 [24] 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. [25] Type 2 diabetes may be preceded in its onset by impaired cognitive functioning. [26]

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. [27]

Phenylketonuria, also known as PKU, can induce neurodevelopmental problems and children with PKU require a strict diet to prevent intellectual disability 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 intellectual disability and other disorders. [28] [29]

Nutrition

Nutrition disorders and nutritional deficits may cause neurodevelopmental disorders, such as spina bifida, and the rarely occurring anencephaly, both of which are neural tube defects with malformation and dysfunction of the nervous system and its supporting structures, leading to serious physical disability and emotional sequelae. The most common nutritional cause of neural tube defects is folic acid deficiency in the mother, a B vitamin usually found in fruits, vegetables, whole grains, and milk products. [30] [31] (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.) [32] [33] Another deficiency, iodine deficiency, produces a spectrum of neurodevelopmental disorders ranging from mild emotional disturbance to severe intellectual disability. (see also congenital iodine deficiency syndrome). [34]

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, now called fetal alcohol syndrome, It has significant symptom overlap with several other entirely unrelated neurodevelopmental disorders. [35]

Physical trauma

CT scan showing epidural hematoma, a type of traumatic brain injury (upper left) Epidural hematoma.png
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) [36] of neurodevelopmental syndromes. It may be subdivided into two major categories, congenital injury (including injury resulting from otherwise uncomplicated premature birth) [37] 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. [38]

Placenta

Although it not clear yet as strong is the correlation between placenta and brain, a growing number of studies are linking placenta to fetal brain development. [39]

Diagnosis

Neurodevelopmental disorders are diagnosed by evaluating the presence of characteristic symptoms or behaviors in a child, typically after a parent, guardian, teacher, or other responsible adult has raised concerns to a doctor. [40]

Neurodevelopmental disorders may also be confirmed by genetic testing. Traditionally, disease related genetic and genomic factors are detected by karyotype analysis, which detects clinically significant genetic abnormalities for 5% of children with a diagnosed disorder. As of 2017, chromosomal microarray analysis (CMA) was proposed to replace karyotyping because of its ability to detect smaller chromosome abnormalities and copy-number variants, leading to greater diagnostic yield in about 20% of cases. [18] The American College of Medical Genetics and Genomics and the American Academy of Pediatrics recommend CMA as standard of care in the US. [18]

Management

See also

Related Research Articles

<span class="mw-page-title-main">Williams syndrome</span> Medical condition

Williams syndrome (WS), also Williams–Beuren syndrome (WBS), is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people with WS, with particular challenges with visual spatial tasks such as drawing. Verbal skills are relatively unaffected. Many people with WS have an outgoing personality, an openness to engaging with other people, and a happy disposition. Medical issues with teeth, heart problems, and periods of high blood calcium are common.

<span class="mw-page-title-main">Lissencephaly</span> Medical condition

Lissencephaly is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in a lack of development of brain folds (gyri) and grooves (sulci). It is a form of cephalic disorder. Terms such as agyria and pachygyria are used to describe the appearance of the surface of the brain.

<span class="mw-page-title-main">Megalencephaly</span> Medical condition

Megalencephaly is a growth development disorder in which the brain is abnormally large. It is characterized by a brain with an average weight that is 2.5 standard deviations above the mean of the general population. Approximately 1 out of 50 children (2%) are said to have the characteristics of megalencephaly in the general population.

<span class="mw-page-title-main">Microcephaly</span> Condition in which the head is small due to an underdeveloped brain

Microcephaly is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it may develop in the first few years of life. Brain development is often affected; people with this disorder often have an intellectual disability, poor motor function, poor speech, abnormal facial features, seizures and dwarfism.

<span class="mw-page-title-main">Macrocephaly</span> Abnormally large head size

Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to determine whether the syndrome is accompanied by particular disorders. Those with benign or familial macrocephaly are considered to have megalencephaly.

<span class="mw-page-title-main">Septo-optic dysplasia</span> Medical condition

Septo-optic dysplasia (SOD), known also as de Morsier syndrome, is a rare congenital malformation syndrome that features a combination of the underdevelopment of the optic nerve, pituitary gland dysfunction, and absence of the septum pellucidum . Two or more of these features need to be present for a clinical diagnosis—only 30% of patients have all three. French-Swiss doctor Georges de Morsier first recognized the relation of a rudimentary or absent septum pellucidum with hypoplasia of the optic nerves and chiasm in 1956.

<span class="mw-page-title-main">Birth defect</span> Condition present at birth regardless of cause

A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders.

<span class="mw-page-title-main">Unibrow</span> Presence of abundant hair between the eyebrows

A unibrow is a single eyebrow created when the two eyebrows meet in the middle above the bridge of the nose. The hair above the bridge of the nose is of the same color and thickness as the eyebrows, such that they converge to form one uninterrupted line of hair.

Hypotonia is a state of low muscle tone, often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles. Severe hypotonia in infancy is commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation.

Nonverbal learning disability (NVLD) is a proposed category of neurodevelopmental disorder characterized by core deficits in visual-spatial processing and a significant discrepancy between verbal and nonverbal intelligence. A review of papers found that proposed diagnostic criteria were inconsistent. Proposed additional diagnostic criteria include intact verbal intelligence, and deficits in the following: visuoconstruction abilities, speech prosody, fine motor coordination, mathematical reasoning, visuospatial memory and social skills. NVLD is not recognised by the DSM-5 and is not clinically distinct from learning disorder.

A delayed milestone, which is also known as a developmental delay, refers to a situation where a child does not reach a particular developmental milestone at the expected age. Developmental milestones refer to a collection of indicators that a child is anticipated to reach as they grow older.

<span class="mw-page-title-main">Causes of autism</span> Proposed causes of autism

Many causes of autism, including environmental and genetic factors, have been recognized or proposed, but understanding of the theory of causation of autism is incomplete. Attempts have been made to incorporate the known genetic and environmental causes into a comprehensive causative framework. ASD is a neurodevelopmental disorder marked by impairments in communicative ability and social interaction and restricted/repetitive behaviors, interests, or activities not suitable for the individual's developmental stage. The severity of symptoms and functional impairment vary between individuals.

<span class="mw-page-title-main">Central nervous system disease</span> Disease of the brain or spinal cord

Central nervous system diseases or central nervous system disorders are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS). These disorders may be caused by such things as infection, injury, blood clots, age related degeneration, cancer, autoimmune disfunction, and birth defects. The symptoms vary widely, as do the treatments.

<span class="mw-page-title-main">Intellectual disability</span> Generalized neurodevelopmental disorder

Intellectual disability (ID), also known as general learning disability and mental retardation, is a generalized neurodevelopmental disorder characterized by significant impairment in intellectual and adaptive functioning that is first apparent during childhood. Children with intellectual disabilities typically have an intelligence quotient (IQ) below 70 and deficits in at least two adaptive behaviors that affect everyday, general living. According to the DSM-5, intellectual functions include reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience. Deficits in these functions must be confirmed by clinical evaluation and individualized standard IQ testing. On the other hand, adaptive behaviors include the social, developmental, and practical skills people learn to perform tasks in their everyday lives. Deficits in adaptive functioning often compromises an individual's independence and ability to meet their social responsibility.

<span class="mw-page-title-main">Angelman syndrome</span> Genetic disorder caused by part of the mothers chromosome 15 being missing

Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.

<span class="mw-page-title-main">Neurological disorder</span> Any disorder of the nervous system

A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor coordination, loss of sensation, seizures, confusion, pain, tauopathies, and altered levels of consciousness. There are many recognized neurological disorders, some relatively common, but many rare. They may be assessed by neurological examination, and studied and treated within the specialties of neurology and clinical neuropsychology.

Mental disorders diagnosed in childhood can be neurodevelopmental, emotional, or behavioral disorders. These disorders negatively impact the mental and social wellbeing of a child, and children with these disorders require support from their families and schools. Childhood mental disorders often persist into adulthood. These disorders are usually first diagnosed in infancy, childhood, or adolescence, as laid out in the DSM-5 and in the ICD-11.

Global developmental delay is an umbrella term used when children are significantly delayed in two or more areas of development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, cognitive skills, and social and emotional development. There is usually a specific condition which causes this delay, such as Cerebral Palsy, Fragile X syndrome or other chromosomal abnormalities. However, it is sometimes difficult to identify this underlying condition.

The RASopathies are a group of developmental syndromes caused by germline mutations in genes belonging to the Ras/MAPK pathway. Common features include intellectual disability, congenital heart defects, skin abnormalities, and craniofacial abnormalities.

<span class="mw-page-title-main">Salt and pepper syndrome</span> Medical condition

Salt and pepper developmental regression syndrome, also known as Amish infantile epileptic syndrome or GM3 deficiency syndrome, is a rare autosomal recessive progressive neurological disorder characterized by developmental delay, severe intellectual disability, seizures, and skin pigmentation irregularities. The clinical symptoms of this condition start manifesting soon after birth, during the newborn/neo-natal stage of life.

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  38. ↑ Collins KA, Popek E (December 2018). "Birth Injury: Birth Asphyxia and Birth Trauma". Academic Forensic Pathology. 8 (4): 788–864. doi:10.1177/1925362118821468. PMC   6491540 . PMID   31240076.
  39. ↑ Kratimenos P, Penn AA (August 2019). "Placental programming of neuropsychiatric disease". Pediatric Research. 86 (2): 157–164. doi: 10.1038/s41390-019-0405-9 . PMID   31003234. S2CID   124094051.
  40. ↑ Neurodevelopmental Disorders (PDF), America's Children and the Environment (3 ed.), EPA, August 2017, p. 12, archived (PDF) from the original on 2021-07-20, retrieved 2019-07-10

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