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Neurodevelopmental disorder

Topic: Medicine

 From HandWiki - Reading time: 18 min

Short description: Set of disorders affecting development of nervous system

Neurodevelopmental disorder
SpecialtyPsychiatry, neurology
SymptomsImpaired in personal, social, academic domains
Usual onsetEarly childhood (typically before school age)
Types
Diagnostic methodClinical symptom evaluation, may be confirmed by genetic testing
TreatmentEarly intervention, therapy, educational support

Neurodevelopmental disorders (NDDs) are a diverse group of complex conditions thought to be caused by the abnormal development of the brain, or by injury or infection during child development.[1][2][3] These conditions generally appear in early childhood, usually pre-school age, and can persist into adulthood.[4][3]

Neurodevelopmental disorders are categorized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 2013 (DSM-5) into six groups: intellectual disabilities, communication disorders, autism spectrum disorder, attention deficit hyperactivity disorder, motor disorders, and specific learning disorders.[3] The international classification of diseases ICD-11 published by the World Health Organisation (WHO), includes NDDs in the general heading of Mental, behavioral or neurodevelopmental disorders, and lists them in seven groupings.[1]

More than one NDD may be present, giving overlapping symptoms, and are often complicated by the co-occurrence of other conditions.[2][3] For instance a tic disorder a type of motor disorder may also be comorbid with a movement disorder, a mental disorder, or a substance use disorder.[5]

Some NDDs such as Down syndrome have a genetic cause. Other possible causes include environmental factors such as prenatal stress, early developmental stress, and fetal exposure to neurotoxins; pollution, infections,[6][7][8] and traumatic brain injury.[9][10]

NDDs are diverse and treatment will be aimed at the disorder.

Classification

Neurodevelopment disorders (NDDs) are diverse and complex. Neurodevelopment itself is a wide-ranging process prone to abnormalities that may be responsible for the early presentation of the intellectual and functional impairments of the NDDs. Symptoms of an NDD may often overlap with another condition (including another NDD) making diagnosis and appropriate treatment a challenge.[2][3] The six groups of disorders categorised by DSM5 are intellectual disability, communication disorder, autism, attention deficit hyperactivity disorder, motor disorders, and specific learning disorders.[3]

Intellectual disability

Intellectual disability, also disorder of intellectual development,[11] and known as learning difficulty (in the United Kingdom and different from learning disability),[12] formerly mental retardation, is a neurodevelopmental disorder characterized by significant impairment in intellectual and adaptive functioning.[13][14][15] The level of impairment may be mild, moderate, severe or profound.[3][11] Causes may be either developmental or genetic. Children with intellectual disability typically have an intelligence quotient (IQ) below 70 and deficits in at least two adaptive behaviors that affect everyday living.

Communication disorders

A communication disorder is any disorder that affects an individual's ability to comprehend, detect, or apply language and speech to engage in dialogue effectively with others.[16] This also encompasses deficiencies in verbal and non-verbal communication styles.[17] The delays and disorders can range from simple sound substitution to the inability to understand or use one's native language.[18]

Autism spectrum disorder

Autism, also known as autism spectrum disorder (ASD), is a condition characterized by impairment in social communication and interaction,[19][20] as well as a need or strong preference for predictability and routine, sensory processing differences, focused interests, or repetitive behaviors. Features of autism are present from early childhood and the condition typically persists throughout life.[21][22] Autism is classified as a neurodevelopmental disorder,[23] and a diagnosis requires professional assessment that these characteristics cause significant challenges in daily life beyond what is expected given a person's age and social environment.[24][25][26][19] Because autism is a spectrum disorder, presentations vary and support needs range from minimal assistance to full-time, 24-hour care.[25][19][27][28]

Attention deficit hyperactivity disorder

Main article: Medicine:Attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by executive dysfunction occasioning symptoms of inattention, hyperactivity, impulsivity and emotional dysregulation that are excessive and pervasive, impairing in multiple contexts, and developmentally-inappropriate.[29][30][31]

ADHD symptoms arise from executive dysfunction,[40] and emotional dysregulation is often considered a core symptom.[44] Difficulties in self-regulation such as time management, inhibition and sustained attention may cause poor professional performance, relationship difficulties and numerous health risks,[45][46] collectively predisposing to a diminished quality of life[47] and a direct average reduction in life expectancy of 13 years.[48][49] ADHD is associated with other neurodevelopmental and mental disorders as well as non-psychiatric disorders, which can cause additional impairment.[31]

Motor disorders

Motor disorders are neurodevelopmental disorders that cause abnormal and involuntary movements. They can result from damage to the motor system. They were redefined in DSM-5.[50] Motor disorders include developmental coordination disorder, stereotypic movement disorder, and tic disorders including Tourette's.[50] Motor disorders are distinct from movement disorders.

Developmental coordination disorder

Developmental coordination disorder is an impaired coordination that results from impaired motor planning.

Stereotypic movement disorder

Stereotypic movement disorder displays restrictive or repetitive movements such as hand waving or head banging that are prolonged and intense causing significant impairment.

Specific learning disorders

Deficits in any area of information processing can manifest in a variety of specific learning disabilities (SLD). It is possible for an individual to have more than one of these difficulties. This is referred to as comorbidity or co-occurrence of learning disabilities.[51]

Nonverbal learning disorder

Nonverbal learning disorder is a suggested syndrome as a subtype of specific learning disorder. Nonverbal learning disorder involves an impairment in visuospatial abilities making it difficult to process nonverbal information such as presented in maths.[52][53][54][55] This proposed subtype also implicates an impaired sense of touch.[52] Whilst it has been recognised for many years it is not an official diagnosis. A proposed reframing to Developmental visual-spatial disorder is hoped to be accepted as a disorder in the DSM.[56]

Causes

The development of the nervous system (neurodevelopment), 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.[57] 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.[58] Some deficits may be predicted from observed deviations in the maturation patterns of the infant gut microbiome.[59]

Social deprivation

Deprivation from social and emotional care causes severe delays in brain and cognitive development.[60] 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.[61]

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,[62] 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).[63]

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".[64] Rett syndrome, another X-linked disorder, produces severe functional limitations.[65] Williams syndrome is caused by small deletions of genetic material from chromosome 7.[66] The most common recurrent copy number variation disorder is DiGeorge syndrome (22q11.2 deletion syndrome), followed by Prader-Willi syndrome and Angelman syndrome.[67]

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,[68] or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection.[69] 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,[70] so sometimes several family members may have one or both of them following an epidemic of Strep infection.

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[71] 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[71] 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.[72]

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[73] 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.[74] Type 2 diabetes may be preceded in its onset by impaired cognitive functioning.[75]

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.[76]

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.[77][78]

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.[79][80] (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.)[81] 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).[82]

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.[83]

Physical trauma

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)[84] of neurodevelopmental syndromes. It may be subdivided into two major categories, congenital injury (including injury resulting from otherwise uncomplicated premature birth)[85] 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.[86]

Placenta

Although it is not clear yet how strong the connection between placenta and brain is, a growing number of studies are linking the placenta to fetal brain development.[87]

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.[88]

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.[67] The American College of Medical Genetics and Genomics and the American Academy of Pediatrics recommend CMA as standard of care in the US.[67]

See also

References

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  2. ↑ 2.0 2.1 2.2 "Neurodevelopmental Disorders (NDDs): Beyond the Clinical Definition and Translational Approach". Children (Basel) 10 (1): 99. January 2023. doi:10.3390/children10010099. PMID 36670649. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). Washington, D.C.: American Psychiatric Association. 2013. pp. 31–33. ISBN 978-0-89042-554-1. 
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  5. ↑ Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). Washington, D.C.: American Psychiatric Association. 2013. p. 85. ISBN 978-0-89042-554-1. 
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  70. ↑ "Genetics of childhood disorders: XXXIII. Autoimmunity, part 6: poststreptococcal autoimmunity". Journal of the American Academy of Child and Adolescent Psychiatry 40 (12): 1479–1482. December 2001. doi:10.1097/00004583-200112000-00021. PMID 11765296. http://www.med.yale.edu/chldstdy/plomdevelop/genetics/01decgen.htm. Retrieved 2008-08-17. 
  71. ↑ 71.0 71.1 "Reducing neurodevelopmental disorders and disability through research and interventions". Nature 527 (7578): S155–S160. November 2015. doi:10.1038/nature16029. PMID 26580321. Bibcode: 2015Natur.527S.155B. 
  72. ↑ "Prenatal infection as a risk factor for schizophrenia". Schizophrenia Bulletin 32 (2): 200–202. April 2006. doi:10.1093/schbul/sbj052. PMID 16469941. 
  73. ↑ "Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum". Prostaglandins, Leukotrienes, and Essential Fatty Acids 63 (1–2): 1–9. July 2000. doi:10.1054/plef.2000.0184. PMID 10970706. 
  74. ↑ "Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset". Diabetes Care 24 (9): 1541–1546. September 2001. doi:10.2337/diacare.24.9.1541. PMID 11522696. 
  75. ↑ "Cognitive function in children and subsequent type 2 diabetes". Diabetes Care 31 (3): 514–516. March 2008. doi:10.2337/dc07-1399. PMID 18083794. 
  76. ↑ "Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes". Archives of Disease in Childhood. Fetal and Neonatal Edition 81 (1): F10–F14. July 1999. doi:10.1136/fn.81.1.F10. PMID 10375355. 
  77. ↑ "Maternal phenylketonuria: report from the United Kingdom Registry 1978-97". Archives of Disease in Childhood 90 (2): 143–146. February 2005. doi:10.1136/adc.2003.037762. PMID 15665165. 
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  79. ↑ "Folic Acid". March of Dimes. http://www.marchofdimes.org/pregnancy/folic-acid.aspx. 
  80. ↑ "Folate (Folacin, Folic Acid)". Ohio State University Extension. http://ohioline.osu.edu/hyg-fact/5000/5553.html. 
  81. ↑ "Folic scid: topic home". Centers for Disease Control and Prevention. U.S. Department of Health and Human Services. https://www.cdc.gov/ncbddd/folicacid/. 
  82. ↑ "Iodine deficiency in pregnancy: the effect on neurodevelopment in the child". Nutrients 3 (2): 265–273. February 2011. doi:10.3390/nu3020265. PMID 22254096. 
  83. ↑ Fetal alcohol syndrome: guidelines for referral and diagnosis (PDF). CDC (July 2004). Retrieved on 2007-04-11
  84. ↑ "Facts About TBI". U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/ncipc/tbi/FactSheets/Facts_About_TBI.pdf. 
  85. ↑ "Is schizophrenia a neurodevelopmental disorder?". British Medical Journal 295 (6600): 681–682. September 1987. doi:10.1136/bmj.295.6600.681. PMID 3117295. 
  86. ↑ "Birth Injury: Birth Asphyxia and Birth Trauma". Academic Forensic Pathology 8 (4): 788–864. December 2018. doi:10.1177/1925362118821468. PMID 31240076. 
  87. ↑ "Placental programming of neuropsychiatric disease". Pediatric Research 86 (2): 157–164. August 2019. doi:10.1038/s41390-019-0405-9. PMID 31003234. 
  88. ↑ Neurodevelopmental Disorders, America's Children and the Environment (3 ed.), EPA, August 2017, p. 12, https://www.epa.gov/sites/default/files/2017-07/documents/neurodevelopmental_updates_0.pdf, retrieved 2019-07-10 

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