Neurodevelopmental disorder

Intellectual disability, also known as general learning disability is a disorder that affects the ability to learn, retain, or process information; to think critically or abstractly, and to solve problems. Adaptive behaviour is limited, affecting daily living activities. Global developmental delay is categorized under intellectual disability and is diagnosed when several areas of intellectual functioning are affected.{{cite book |title=Diagnostic and statistical manual of mental disorders: DSM-5 |date=2013 |publisher=American Psychiatric Association |location=Washington, D.C. |isbn=978-0-89042-554-1 |pages=58–65 |edition=5th}}

{{main|Communication disorder}}

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.Collins, John William. "The greenwood dictionary of education". Greenwood, 2011. page 86. {{ISBN|978-0-313-37930-7}} This also encompasses deficiencies in verbal and nonverbal communication styles.{{Cite web |date=1993 |title=Definitions of Communication Disorders and Variations |url=https://www.asha.org/policy/rp1993-00208/ |access-date=2023-11-07 |website=American Speech-Language-Hearing Association |language=en}} Examples include stuttering, sound substitution, inability to understand or use one's native language.{{cite book |author=Gleason, Jean Berko |title=The development of language |publisher=Allyn and Bacon |location=Boston |year=2001 |isbn=978-0-205-31636-6 |oclc=43694441 |url-access=registration |url=https://archive.org/details/developmentoflan00glea }}

{{main|Autism}}

Autism, also called autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder characterized by symptoms of deficient reciprocal social communication and the presence of restricted, repetitive, and inflexible patterns of behavior. While its severity and specific manifestations vary widely across the spectrum, autism generally affects a person's ability to understand and connect with others and adapt to everyday situations. Like most developmental disorders, autism exists along a continuum of symptom severity, subjective distress, and functional impairment. A consequence of this dimensionality is substantial variability across autistic persons with respect to both the nature and the extent of required supports.

A formal diagnosis of ASD requires not merely the presence of ASD symptoms, but symptoms that cause significant impairment in multiple domains of functioning, in addition to being excessive or atypical enough to be developmentally and socioculturally inappropriate.{{cite web |title=Autism spectrum disorder |url=https://icd.who.int/browse/2024-01/mms/en#437815624 |access-date=8 September 2024}}{{Cite web |title=IACC Subcommittee Diagnostic Criteria - DSM-5 Planning Group {{!}} IACC |url=https://iacc.hhs.gov/about-iacc/subcommittees/resources/dsm5-diagnostic-criteria.shtml |access-date=2024-08-01 |website=iacc.hhs.gov}}

{{main|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.{{cite book |title=Diagnostic and Statistical Manual of Mental Disorders | edition = Fifth, Text Revision (DSM-5-TR) |title-link=DSM-5-TR |publisher=American Psychiatric Publishing |date=February 2022 |isbn=978-0-89042-575-6 |oclc=1288423302 |location=Washington, D.C. }}{{cite journal | vauthors = Foreman DM | title = Attention deficit hyperactivity disorder: legal and ethical aspects | journal = Archives of Disease in Childhood | volume = 91 | issue = 2 | pages = 192–194 | date = February 2006 | pmid = 16428370 | pmc = 2082674 | doi = 10.1136/adc.2004.064576 }}{{cite journal | vauthors = Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, Newcorn JH, Gignac M, Al Saud NM, Manor I, Rohde LA, Yang L, Cortese S, Almagor D, Stein MA, Albatti TH, Aljoudi HF, Alqahtani MM, Asherson P, Atwoli L, Bölte S, Buitelaar JK, Crunelle CL, Daley D, Dalsgaard S, Döpfner M, Espinet S, Fitzgerald M, Franke B, Gerlach M, Haavik J, Hartman CA, Hartung CM, Hinshaw SP, Hoekstra PJ, Hollis C, Kollins SH, Sandra Kooij JJ, Kuntsi J, Larsson H, Li T, Liu J, Merzon E, Mattingly G, Mattos P, McCarthy S, Mikami AY, Molina BS, Nigg JT, Purper-Ouakil D, Omigbodun OO, Polanczyk GV, Pollak Y, Poulton AS, Rajkumar RP, Reding A, Reif A, Rubia K, Rucklidge J, Romanos M, Ramos-Quiroga JA, Schellekens A, Scheres A, Schoeman R, Schweitzer JB, Shah H, Solanto MV, Sonuga-Barke E, Soutullo C, Steinhausen HC, Swanson JM, Thapar A, Tripp G, van de Glind G, van den Brink W, Van der Oord S, Venter A, Vitiello B, Walitza S, Wang Y | title = The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder | journal = Neuroscience and Biobehavioral Reviews | volume = 128 | pages = 789–818 | date = September 2021 | pmid = 33549739 | pmc = 8328933 | doi = 10.1016/j.neubiorev.2021.01.022 | publisher = Elsevier BV | doi-access = free | issn=0149-7634}}

ADHD symptoms arise from executive dysfunction,{{refn|{{cite journal | vauthors = Pievsky MA, McGrath RE | title = The Neurocognitive Profile of Attention-Deficit/Hyperactivity Disorder: A Review of Meta-Analyses | journal = Archives of Clinical Neuropsychology | volume = 33 | issue = 2 | pages = 143–157 | date = March 2018 | pmid = 29106438 | doi = 10.1093/arclin/acx055 | doi-access = free }}{{cite journal | vauthors = Schoechlin C, Engel RR | title = Neuropsychological performance in adult attention-deficit hyperactivity disorder: meta-analysis of empirical data | journal = Archives of Clinical Neuropsychology | volume = 20 | issue = 6 | pages = 727–744 | date = August 2005 | pmid = 15953706 | doi = 10.1016/j.acn.2005.04.005 }}{{cite journal | vauthors = Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K | title = Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects | journal = JAMA Psychiatry | volume = 70 | issue = 2 | pages = 185–198 | date = February 2013 | pmid = 23247506 | doi = 10.1001/jamapsychiatry.2013.277 }}{{cite journal | vauthors = Hoogman M, Muetzel R, Guimaraes JP, Shumskaya E, Mennes M, Zwiers MP, Jahanshad N, Sudre G, Wolfers T, Earl EA, Soliva Vila JC, Vives-Gilabert Y, Khadka S, Novotny SE, Hartman CA, Heslenfeld DJ, Schweren LJ, Ambrosino S, Oranje B, de Zeeuw P, Chaim-Avancini TM, Rosa PG, Zanetti MV, Malpas CB, Kohls G, von Polier GG, Seitz J, Biederman J, Doyle AE, Dale AM, van Erp TG, Epstein JN, Jernigan TL, Baur-Streubel R, Ziegler GC, Zierhut KC, Schrantee A, Høvik MF, Lundervold AJ, Kelly C, McCarthy H, Skokauskas N, O'Gorman Tuura RL, Calvo A, Lera-Miguel S, Nicolau R, Chantiluke KC, Christakou A, Vance A, Cercignani M, Gabel MC, Asherson P, Baumeister S, Brandeis D, Hohmann S, Bramati IE, Tovar-Moll F, Fallgatter AJ, Kardatzki B, Schwarz L, Anikin A, Baranov A, Gogberashvili T, Kapilushniy D, Solovieva A, El Marroun H, White T, Karkashadze G, Namazova-Baranova L, Ethofer T, Mattos P, Banaschewski T, Coghill D, Plessen KJ, Kuntsi J, Mehta MA, Paloyelis Y, Harrison NA, Bellgrove MA, Silk TJ, Cubillo AI, Rubia K, Lazaro L, Brem S, Walitza S, Frodl T, Zentis M, Castellanos FX, Yoncheva YN, Haavik J, Reneman L, Conzelmann A, Lesch KP, Pauli P, Reif A, Tamm L, Konrad K, Oberwelland Weiss E, Busatto GF, Louza MR, Durston S, Hoekstra PJ, Oosterlaan J, Stevens MC, Ramos-Quiroga JA, Vilarroya O, Fair DA, Nigg JT, Thompson PM, Buitelaar JK, Faraone SV, Shaw P, Tiemeier H, Bralten J, Franke B | title = Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples | journal = The American Journal of Psychiatry | volume = 176 | issue = 7 | pages = 531–542 | date = July 2019 | pmid = 31014101 | pmc = 6879185 | doi = 10.1176/appi.ajp.2019.18091033 }}{{cite journal | vauthors = Brown TE | title = ADD/ADHD and Impaired Executive Function in Clinical Practice | journal = Current Psychiatry Reports | volume = 10 | issue = 5 | pages = 407–411 | date = October 2008 | pmid = 18803914 | doi = 10.1007/s11920-008-0065-7 | s2cid = 146463279 }}{{cite book |title=Molecular Neuropharmacology: A Foundation for Clinical Neuroscience |vauthors=Malenka RC, Nestler EJ, Hyman SE |publisher=McGraw-Hill Medical |year=2009 |isbn=978-0-07-148127-4 |veditors=Sydor A, Brown RY |edition=2nd |location=New York |pages=266, 315, 318–323 |chapter=Chapters 10 and 13 |quote=Early results with structural MRI show thinning of the cerebral cortex in ADHD subjects compared with age-matched controls in prefrontal cortex and posterior parietal cortex, areas involved in working memory and attention.}}{{cite journal | vauthors = Diamond A | title = Executive functions | journal = Annual Review of Psychology | volume = 64 | pages = 135–168 | year = 2013 | pmid = 23020641 | pmc = 4084861 | doi = 10.1146/annurev-psych-113011-143750 | quote = {{abbr|EFs|executive functions}} and prefrontal cortex are the first to suffer, and suffer disproportionately, if something is not right in your life. They suffer first, and most, if you are stressed (Arnsten 1998, Liston et al. 2009, Oaten & Cheng 2005), sad (Hirt et al. 2008, von Hecker & Meiser 2005), lonely (Baumeister et al. 2002, Cacioppo & Patrick 2008, Campbell et al. 2006, Tun et al. 2012), sleep deprived (Barnes et al. 2012, Huang et al. 2007), or not physically fit (Best 2010, Chaddock et al. 2011, Hillman et al. 2008). Any of these can cause you to appear to have a disorder of EFs, such as ADHD, when you do not. }}{{cite book | vauthors = Antshel KM, Hier BO, Barkley RA | chapter = Executive Functioning Theory and ADHD |date=2014 | title = Handbook of Executive Functioning |pages=107–120 | veditors = Goldstein S, Naglieri JA |place=New York, NY |publisher=Springer |doi=10.1007/978-1-4614-8106-5_7 |isbn=978-1-4614-8106-5 }}}} and emotional dysregulation is often considered a core symptom.{{refn|{{cite journal | vauthors = Retz W, Stieglitz RD, Corbisiero S, Retz-Junginger P, Rösler M | title = Emotional dysregulation in adult ADHD: What is the empirical evidence? | journal = Expert Review of Neurotherapeutics | volume = 12 | issue = 10 | pages = 1241–1251 | date = October 2012 | pmid = 23082740 | doi = 10.1586/ern.12.109 | s2cid = 207221320 }}{{cite journal | vauthors = Faraone SV, Rostain AL, Blader J, Busch B, Childress AC, Connor DF, Newcorn JH | title = Practitioner Review: Emotional dysregulation in attention-deficit/hyperactivity disorder - implications for clinical recognition and intervention | journal = Journal of Child Psychology and Psychiatry, and Allied Disciplines | volume = 60 | issue = 2 | pages = 133–150 | date = February 2019 | pmid = 29624671 | doi = 10.1111/jcpp.12899 }}{{cite journal | vauthors = Shaw P, Stringaris A, Nigg J, Leibenluft E | title = Emotion dysregulation in attention deficit hyperactivity disorder | journal = The American Journal of Psychiatry | volume = 171 | issue = 3 | pages = 276–293 | date = March 2014 | pmid = 24480998 | pmc = 4282137 | doi = 10.1176/appi.ajp.2013.13070966 }}}} Difficulties in self-regulation such as time management, inhibition and sustained attention may cause poor professional performance, relationship difficulties and numerous health risks,{{Cite journal | vauthors = Barkley RA, Murphy KR |date=2011-06-01 |title=The Nature of Executive Function (EF) Deficits in Daily Life Activities in Adults with ADHD and Their Relationship to Performance on EF Tests |url=https://doi.org/10.1007/s10862-011-9217-x |journal=Journal of Psychopathology and Behavioral Assessment |language=en |volume=33 |issue=2 |pages=137–158 |doi=10.1007/s10862-011-9217-x |issn=1573-3505}}{{cite journal | vauthors = Fleming M, Fitton CA, Steiner MF, McLay JS, Clark D, King A, Mackay DF, Pell JP | title = Educational and Health Outcomes of Children Treated for Attention-Deficit/Hyperactivity Disorder | journal = JAMA Pediatrics | volume = 171 | issue = 7 | pages = e170691 | date = July 2017 | pmid = 28459927 | pmc = 6583483 | doi = 10.1001/jamapediatrics.2017.0691 }} collectively predisposing to a diminished quality of life{{cite journal | vauthors = Lee YC, Yang HJ, Chen VC, Lee WT, Teng MJ, Lin CH, Gossop M | title = Meta-analysis of quality of life in children and adolescents with ADHD: By both parent proxy-report and child self-report using PedsQL™ | journal = Research in Developmental Disabilities | volume = 51-52 | pages = 160–172 | date = 2016-04-01 | pmid = 26829402 | doi = 10.1016/j.ridd.2015.11.009 }} and a direct average reduction in life expectancy of 13 years.{{cite journal | vauthors = Barkley RA, Fischer M | title = Hyperactive Child Syndrome and Estimated Life Expectancy at Young Adult Follow-Up: The Role of ADHD Persistence and Other Potential Predictors | journal = Journal of Attention Disorders | volume = 23 | issue = 9 | pages = 907–923 | date = July 2019 | pmid = 30526189 | doi = 10.1177/1087054718816164 | s2cid = 54472439 }}{{cite journal | vauthors = Cattoi B, Alpern I, Katz JS, Keepnews D, Solanto MV | title = The Adverse Health Outcomes, Economic Burden, and Public Health Implications of Unmanaged Attention Deficit Hyperactivity Disorder (ADHD): A Call to Action Resulting from CHADD Summit, Washington, DC, October 17, 2019 | journal = Journal of Attention Disorders | volume = 26 | issue = 6 | pages = 807–808 | date = April 2022 | pmid = 34585995 | doi = 10.1177/10870547211036754 | s2cid = 238218526 }} ADHD is associated with other neurodevelopmental and mental disorders as well as non-psychiatric disorders, which can cause additional impairment.

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

{{main|Learning disability#By function impaired}}

Deficits in any area of information processing can manifest in a variety of {{anchor|specific learning disabilities}} 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.{{Cite AV media |url=https://www.youtube.com/watch?v=dXhO3-S1L-o |title=Dyslexia, Dyspraxia & Overlapping Learning Difficulties |date=2011-10-26 |last=Kirby |first=Amanda |author-link=Amanda Kirby |access-date=2024-11-29 |via=YouTube}}

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.{{cite book|vauthors=Mammarella IC, Cornoldi C|title=Neurocognitive Development: Disorders and Disabilities |date=2020|chapter=Nonverbal learning disability (developmental visuospatial disorder)|series=Handbook of Clinical Neurology|volume=174|pages=83–91|doi=10.1016/B978-0-444-64148-9.00007-7|isbn=9780444641489|pmid=32977898|s2cid=221939377}}{{Cite journal|vauthors=Incháustegui MV|date=2019-06-18|title=Nonverbal Learning Disabilities (Nld) – Clinical Description about Neurodevelopmental Disabilities|journal=Archives in Neurology & Neuroscience|volume=4|issue=1|doi=10.33552/ANN.2019.04.000579|doi-access=free}}{{cite book|title=Neurocognitive Development: Disorders and Disabilities|vauthors=Mammarella IC, Cornoldi C|date=2020|publisher=Elsevier|isbn=978-0-444-64148-9|series=Handbook of Clinical Neurology|volume=174|pages=83–91|language=en|chapter=Nonverbal learning disability (developmental visuospatial disorder)|doi=10.1016/b978-0-444-64148-9.00007-7|pmid=32977898|s2cid=221939377}} While Nonverbal learning disorder is not categorized in the ICD or DSM as a discrete classification, "the majority of researchers and clinicians agree that the profile of NLD clearly exists (but see Spreen, 2011, for an exception{{cite journal | vauthors = Spreen O | title = Nonverbal learning disabilities: a critical review | journal = Child Neuropsychology | volume = 17 | issue = 5 | pages = 418–443 | date = September 2011 | pmid = 21462003 | doi = 10.1080/09297049.2010.546778 | url = http://www.tandfonline.com/doi/abs/10.1080/09297049.2010.546778 | access-date = 2021-04-29 | url-status = live | s2cid = 31974898 | archive-url = https://web.archive.org/web/20210720185432/https://www.tandfonline.com/doi/abs/10.1080/09297049.2010.546778 | archive-date = 2021-07-20 }}), but they disagree on the need for a specific clinical category and on the criteria for its identification."{{cite journal | vauthors = Mammarella IC, Cornoldi C | title = An analysis of the criteria used to diagnose children with Nonverbal Learning Disability (NLD) | journal = Child Neuropsychology | volume = 20 | issue = 3 | pages = 255–280 | date = 2014-05-04 | pmid = 23705673 | doi = 10.1080/09297049.2013.796920 | hdl-access = free | s2cid = 34107811 | hdl = 11577/2668053 }}

The multitude of neurodevelopmental disorders spans 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.

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.{{cite journal | vauthors = Pletikos M, Sousa AM, Sedmak G, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N | display-authors = 6 | title = Temporal specification and bilaterality of human neocortical topographic gene expression | journal = Neuron | volume = 81 | issue = 2 | pages = 321–332 | date = January 2014 | pmid = 24373884 | pmc = 3931000 | doi = 10.1016/j.neuron.2013.11.018 }} 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.{{cite journal | vauthors = Samaco RC, Hogart A, LaSalle JM | title = Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3 | journal = Human Molecular Genetics | volume = 14 | issue = 4 | pages = 483–492 | date = February 2005 | pmid = 15615769 | pmc = 1224722 | doi = 10.1093/hmg/ddi045 }} Some deficits may be predicted from observed deviations in the maturation patterns of the infant gut microbiome.{{Cite journal |last1=Sizemore |first1=Nicholas |last2=Oliphant |first2=Kaitlyn |last3=Zheng |first3=Ruolin |last4=Martin |first4=Camilia R. |last5=Claud |first5=Erika C. |last6=Chattopadhyay |first6=Ishanu |date=2024-04-12 |title=A digital twin of the infant microbiome to predict neurodevelopmental deficits |journal=Science Advances |language=en |volume=10 |issue=15 |pages=eadj0400 |doi=10.1126/sciadv.adj0400 |issn=2375-2548 |pmc=11006218 |pmid=38598636|bibcode=2024SciA...10J.400S }}

Deprivation from social and emotional care causes severe delays in brain and cognitive development.{{cite journal | vauthors = van IJzendoorn MH, Palacios J, Sonuga-Barke EJ, Gunnar MR, Vorria P, McCall RB, LeMare L, Bakermans-Kranenburg MJ, Dobrova-Krol NA, Juffer F | display-authors = 6 | title = Children in Institutional Care: Delayed Development and Resilience | journal = Monographs of the Society for Research in Child Development | volume = 76 | issue = 4 | pages = 8–30 | date = December 2011 | pmid = 25125707 | pmc = 4130248 | doi = 10.1111/j.1540-5834.2011.00626.x }} 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.{{cite journal | vauthors = Nelson CA, Zeanah CH, Fox NA, Marshall PJ, Smyke AT, Guthrie D | title = Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project | journal = Science | volume = 318 | issue = 5858 | pages = 1937–1940 | date = December 2007 | pmid = 18096809 | doi = 10.1126/science.1143921 | s2cid = 1460630 | bibcode = 2007Sci...318.1937N }}{{Dead link|date=April 2020 |bot=InternetArchiveBot |fix-attempted=yes }}

{{main|Genetic disorder}}

Image:Child piggyback2.jpg]]

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,{{Cite journal| vauthors = Diamandopoulos K, Green J |date=October 2018|title=Down syndrome: An integrative review|journal=Journal of Neonatal Nursing|volume=24|issue=5|pages=235–241|doi=10.1016/j.jnn.2018.01.001|s2cid=57620027}} 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).{{cite web |title=Facts about down syndrome |url=http://www.nads.org/pages_new/facts.html |archive-url=https://web.archive.org/web/20120403162637/http://www.nads.org/pages_new/facts.html |archive-date=2012-04-03 |work=National Association of Down Syndrome}}

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".{{cite journal | vauthors = Martin JP, Bell J | title = A Pedigree of Mental Defect Showing Sex-Linkage | journal = Journal of Neurology and Psychiatry | volume = 6 | issue = 3–4 | pages = 154–157 | date = July 1943 | pmid = 21611430 | pmc = 1090429 | doi = 10.1136/jnnp.6.3-4.154 }} Rett syndrome, another X-linked disorder, produces severe functional limitations.{{cite journal | vauthors = Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY | title = Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 | journal = Nature Genetics | volume = 23 | issue = 2 | pages = 185–188 | date = October 1999 | pmid = 10508514 | doi = 10.1038/13810 | s2cid = 3350350 }} Williams syndrome is caused by small deletions of genetic material from chromosome 7.{{cite journal | vauthors = Merla G, Howald C, Henrichsen CN, Lyle R, Wyss C, Zabot MT, Antonarakis SE, Reymond A | display-authors = 6 | title = Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes | journal = American Journal of Human Genetics | volume = 79 | issue = 2 | pages = 332–341 | date = August 2006 | pmid = 16826523 | pmc = 1559497 | doi = 10.1086/506371 }}

The most common recurrent copy number variation disorder is DiGeorge syndrome (22q11.2 deletion syndrome), followed by Prader-Willi syndrome and Angelman syndrome.

{{main|Immune-mediated disease}}

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,{{cite journal | vauthors = Pavone P, Bianchini R, Parano E, Incorpora G, Rizzo R, Mazzone L, Trifiletti RR | title = Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection | journal = Pediatric Neurology | volume = 30 | issue = 2 | pages = 107–110 | date = February 2004 | pmid = 14984902 | doi = 10.1016/S0887-8994(03)00413-2 | hdl-access = free | hdl = 2108/194065 }} or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection.{{cite journal | vauthors = Dale RC, Heyman I, Giovannoni G, Church AW | title = Incidence of anti-brain antibodies in children with obsessive-compulsive disorder | journal = The British Journal of Psychiatry | volume = 187 | issue = 4 | pages = 314–319 | date = October 2005 | pmid = 16199788 | doi = 10.1192/bjp.187.4.314 | doi-access = free }} 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,{{cite journal | vauthors = Swedo SE | title = Genetics of childhood disorders: XXXIII. Autoimmunity, part 6: poststreptococcal autoimmunity | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 40 | issue = 12 | pages = 1479–1482 | date = December 2001 | pmid = 11765296 | doi = 10.1097/00004583-200112000-00021 | url = http://www.med.yale.edu/chldstdy/plomdevelop/genetics/01decgen.htm | access-date = 2008-08-17 | url-status = live | archive-url = https://web.archive.org/web/20210720185517/https://medicine.yale.edu/ | archive-date = 2021-07-20 }} so sometimes several family members may have one or both of them following an epidemic of Strep infection.{{citation needed|date=July 2021}}

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{{cite journal | vauthors = Boivin MJ, Kakooza AM, Warf BC, Davidson LL, Grigorenko EL | title = Reducing neurodevelopmental disorders and disability through research and interventions | journal = Nature | volume = 527 | issue = 7578 | pages = S155–S160 | date = November 2015 | pmid = 26580321 | doi = 10.1038/nature16029 | doi-access = free | bibcode = 2015Natur.527S.155B }} 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 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.{{cite journal | vauthors = Brown AS | title = Prenatal infection as a risk factor for schizophrenia | journal = Schizophrenia Bulletin | volume = 32 | issue = 2 | pages = 200–202 | date = April 2006 | pmid = 16469941 | pmc = 2632220 | doi = 10.1093/schbul/sbj052 }}

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{{cite journal | vauthors = Richardson AJ, Ross MA | title = Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum | journal = Prostaglandins, Leukotrienes, and Essential Fatty Acids | volume = 63 | issue = 1–2 | pages = 1–9 | date = July 2000 | pmid = 10970706 | doi = 10.1054/plef.2000.0184 }} 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.{{cite journal | vauthors = Northam EA, Anderson PJ, Jacobs R, Hughes M, Warne GL, Werther GA | title = Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset | journal = Diabetes Care | volume = 24 | issue = 9 | pages = 1541–1546 | date = September 2001 | pmid = 11522696 | doi = 10.2337/diacare.24.9.1541 | doi-access = free }} Type 2 diabetes may be preceded in its onset by impaired cognitive functioning.{{cite journal | vauthors = Olsson GM, Hulting AL, Montgomery SM | title = Cognitive function in children and subsequent type 2 diabetes | journal = Diabetes Care | volume = 31 | issue = 3 | pages = 514–516 | date = March 2008 | pmid = 18083794 | pmc = 2453642 | doi = 10.2337/dc07-1399 }}{{Dead link|date=April 2020 |bot=InternetArchiveBot |fix-attempted=yes }}

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.{{cite journal | vauthors = Ornoy A, Wolf A, Ratzon N, Greenbaum C, Dulitzky M | title = Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 81 | issue = 1 | pages = F10–F14 | date = July 1999 | pmid = 10375355 | pmc = 1720965 | doi = 10.1136/fn.81.1.F10 }}

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.{{cite journal | vauthors = Lee PJ, Ridout D, Walter JH, Cockburn F | title = Maternal phenylketonuria: report from the United Kingdom Registry 1978-97 | journal = Archives of Disease in Childhood | volume = 90 | issue = 2 | pages = 143–146 | date = February 2005 | pmid = 15665165 | pmc = 1720245 | doi = 10.1136/adc.2003.037762 }}{{cite journal | vauthors = Rouse B, Azen C, Koch R, Matalon R, Hanley W, de la Cruz F, Trefz F, Friedman E, Shifrin H | display-authors = 6 | title = Maternal Phenylketonuria Collaborative Study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae | journal = American Journal of Medical Genetics | volume = 69 | issue = 1 | pages = 89–95 | date = March 1997 | pmid = 9066890 | doi = 10.1002/(SICI)1096-8628(19970303)69:1<89::AID-AJMG17>3.0.CO;2-K | name-list-style = vanc }}

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.{{cite web |url=http://www.marchofdimes.org/pregnancy/folic-acid.aspx |title=Folic Acid |work=March of Dimes |access-date=2014-11-10 |archive-date=2021-08-26 |archive-url=https://web.archive.org/web/20210826064834/https://www.marchofdimes.org/pregnancy/folic-acid.aspx |url-status=live }}{{cite web |url=http://ohioline.osu.edu/hyg-fact/5000/5553.html |title=Folate (Folacin, Folic Acid) |work=Ohio State University Extension |access-date=2008-08-06 |archive-date=2021-08-26 |archive-url=https://web.archive.org/web/20210826064835/https://ohioline.osu.edu/search/site/hyg%20fact%205000%205553 |url-status=live }} (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.){{cite web |work=Centers for Disease Control and Prevention |title=Folic scid: topic home |publisher=U.S. Department of Health and Human Services |url=https://www.cdc.gov/ncbddd/folicacid/ |access-date=2008-08-02 |archive-date=2021-08-26 |archive-url=https://web.archive.org/web/20210826064834/https://www.cdc.gov/ncbddd/folicacid/index.html |url-status=live }} 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).{{cite journal | vauthors = Skeaff SA | title = Iodine deficiency in pregnancy: the effect on neurodevelopment in the child | journal = Nutrients | volume = 3 | issue = 2 | pages = 265–273 | date = February 2011 | pmid = 22254096 | pmc = 3257674 | doi = 10.3390/nu3020265 | doi-access = free }}

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.[https://www.cdc.gov/ncbddd/fas/publications/FAS_guidelines_accessible.pdf Fetal alcohol syndrome: guidelines for referral and diagnosis (PDF).] {{Webarchive|url=https://web.archive.org/web/20090423014606/http://www.cdc.gov/ncbddd/fas/publications/FAS_guidelines_accessible.pdf |date=2009-04-23 }} CDC (July 2004). Retrieved on 2007-04-11

{{main|Traumatic brain injury}}

Image:Epidural hematoma.png 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){{Cite web |url=https://www.cdc.gov/ncipc/tbi/FactSheets/Facts_About_TBI.pdf |title=Facts About TBI |work=U.S. Centers for Disease Control and Prevention |access-date=2008-08-06 |archive-date=2021-08-26 |archive-url=https://web.archive.org/web/20210826064932/https://www.cdc.gov/TraumaticBrainInjury/index.html |url-status=live }} of neurodevelopmental syndromes. It may be subdivided into two major categories, congenital injury (including injury resulting from otherwise uncomplicated premature birth){{cite journal | vauthors = Murray RM, Lewis SW | title = Is schizophrenia a neurodevelopmental disorder? | journal = British Medical Journal | volume = 295 | issue = 6600 | pages = 681–682 | date = September 1987 | pmid = 3117295 | pmc = 1247717 | doi = 10.1136/bmj.295.6600.681 }} 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.{{cite journal | vauthors = Collins KA, Popek E | title = Birth Injury: Birth Asphyxia and Birth Trauma | journal = Academic Forensic Pathology | volume = 8 | issue = 4 | pages = 788–864 | date = December 2018 | pmid = 31240076 | pmc = 6491540 | doi = 10.1177/1925362118821468 }}

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.{{cite journal | vauthors = Kratimenos P, Penn AA | title = Placental programming of neuropsychiatric disease | journal = Pediatric Research | volume = 86 | issue = 2 | pages = 157–164 | date = August 2019 | pmid = 31003234 | doi = 10.1038/s41390-019-0405-9 | s2cid = 124094051 | doi-access = free | pmc = 11906117 }}

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.{{citation|title=Neurodevelopmental Disorders|series=America's Children and the Environment|edition=3|pages=12|publisher=EPA|date=August 2017|access-date=2019-07-10|url=https://www.epa.gov/sites/production/files/2017-07/documents/neurodevelopmental_updates_0.pdf|archive-date=2021-07-20|archive-url=https://web.archive.org/web/20210720185345/https://www.epa.gov/sites/default/files/2017-07/documents/neurodevelopmental_updates_0.pdf|url-status=live}}

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.{{cite journal | vauthors = Martin CL, Ledbetter DH | title = Chromosomal Microarray Testing for Children With Unexplained Neurodevelopmental Disorders | journal = JAMA | volume = 317 | issue = 24 | pages = 2545–2546 | date = June 2017 | pmid = 28654998 | pmc = 7058144 | doi = 10.1001/jama.2017.7272 }} The American College of Medical Genetics and Genomics and the American Academy of Pediatrics recommend CMA as standard of care in the US.

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• Developmental disability
• Epigenetics
• Microcephaly
• Teratology
• TRPM3-related neurodevelopmental disorder

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{{refbegin}}

• {{cite book | vauthors = Tager-Flusberg H |title=Neurodevelopmental disorders |publisher=MIT Press |location=Cambridge, Massachusetts |date=1999 |isbn=978-0-262-20116-2 |author-link=Helen Tager-Flusberg }}
• {{cite book | vauthors = Brooks DR, Fleischhacker WW |title=Neurodevelopmental Disorders |publisher=Springer |location=Berlin |date=2006 |isbn=978-3-211-26291-7 }}

{{refend}}

• [http://www.medscape.com/viewarticle/445156 A Review of Neurodevelopmental Disorders] – Medscape review

{{Neuroscience}}

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Category:Neurological disorders