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Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities(NEDASB)

MedGen UID:
1714862
Concept ID:
C5394311
Disease or Syndrome
Synonyms: NEDASB; NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT AUTISTIC FEATURES AND/OR STRUCTURAL BRAIN ABNORMALITIES
 
Gene (location): NOVA2 (19q13.32)
 
Monarch Initiative: MONDO:0030024
OMIM®: 618859

Definition

Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB) is an early-onset neurologic disorder characterized by global developmental delay, poor or absent speech and language development, and behavioral abnormalities reminiscent of autism spectrum disorder (ASD; 209850) or Angelman syndrome (AS; 105830). Additional features may include poor overall growth with small head circumference, axial hypotonia, spasticity, and seizures. Some patients have abnormal findings on brain imaging, including cerebral atrophy, cerebellar atrophy, and/or thin corpus callosum (summary by Mattioli et al., 2020). [from OMIM]

Clinical features

From HPO
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Inappropriate laughter
MedGen UID:
98407
Concept ID:
C0424304
Finding
Laughing that may be excessive and/or inappropriate in context (e.g., laughing at a funeral while others are crying).
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Chiari type I malformation
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line)
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Recurrent hand flapping
MedGen UID:
867996
Concept ID:
C4022387
Mental or Behavioral Dysfunction
A type of repetitive behavior in which the affected individual repeatedly waves the hands and/or arms rhythmically.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Deep philtrum
MedGen UID:
374311
Concept ID:
C1839797
Finding
Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
High anterior hairline
MedGen UID:
477667
Concept ID:
C3276036
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.
Bilateral ptosis
MedGen UID:
356120
Concept ID:
C1865916
Disease or Syndrome

Professional guidelines

PubMed

Rogers JP, Oldham MA, Fricchione G, Northoff G, Ellen Wilson J, Mann SC, Francis A, Wieck A, Elizabeth Wachtel L, Lewis G, Grover S, Hirjak D, Ahuja N, Zandi MS, Young AH, Fone K, Andrews S, Kessler D, Saifee T, Gee S, Baldwin DS, David AS
J Psychopharmacol 2023 Apr;37(4):327-369. Epub 2023 Apr 11 doi: 10.1177/02698811231158232. PMID: 37039129Free PMC Article
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 MMJ, 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 BSG, 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
Neurosci Biobehav Rev 2021 Sep;128:789-818. Epub 2021 Feb 4 doi: 10.1016/j.neubiorev.2021.01.022. PMID: 33549739Free PMC Article
Wolraich ML, Hagan JF Jr, Allan C, Chan E, Davison D, Earls M, Evans SW, Flinn SK, Froehlich T, Frost J, Holbrook JR, Lehmann CU, Lessin HR, Okechukwu K, Pierce KL, Winner JD, Zurhellen W; SUBCOMMITTEE ON CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVE DISORDER
Pediatrics 2019 Oct;144(4) doi: 10.1542/peds.2019-2528. PMID: 31570648Free PMC Article

Recent clinical studies

Etiology

Dawson G, Rieder AD, Johnson MH
Lancet Neurol 2023 Mar;22(3):244-254. Epub 2022 Nov 22 doi: 10.1016/S1474-4422(22)00407-0. PMID: 36427512Free PMC Article
Kawano S, Baba M, Fukushima H, Miura D, Hashimoto H, Nakazawa T
Biochem Biophys Res Commun 2022 May 21;605:45-50. Epub 2022 Mar 12 doi: 10.1016/j.bbrc.2022.03.058. PMID: 35313230
Jones W, Klin A
Nature 2013 Dec 19;504(7480):427-31. Epub 2013 Nov 6 doi: 10.1038/nature12715. PMID: 24196715Free PMC Article
McPartland J, Volkmar FR
Handb Clin Neurol 2012;106:407-18. doi: 10.1016/B978-0-444-52002-9.00023-1. PMID: 22608634Free PMC Article
Arndt TL, Stodgell CJ, Rodier PM
Int J Dev Neurosci 2005 Apr-May;23(2-3):189-99. doi: 10.1016/j.ijdevneu.2004.11.001. PMID: 15749245

Diagnosis

Keski-Rahkonen A, Ruusunen A
Curr Opin Psychiatry 2023 Nov 1;36(6):438-442. Epub 2023 Aug 29 doi: 10.1097/YCO.0000000000000896. PMID: 37781978
Dawson G, Rieder AD, Johnson MH
Lancet Neurol 2023 Mar;22(3):244-254. Epub 2022 Nov 22 doi: 10.1016/S1474-4422(22)00407-0. PMID: 36427512Free PMC Article
Wang SS, Kloth AD, Badura A
Neuron 2014 Aug 6;83(3):518-32. doi: 10.1016/j.neuron.2014.07.016. PMID: 25102558Free PMC Article
McPartland J, Volkmar FR
Handb Clin Neurol 2012;106:407-18. doi: 10.1016/B978-0-444-52002-9.00023-1. PMID: 22608634Free PMC Article
Arndt TL, Stodgell CJ, Rodier PM
Int J Dev Neurosci 2005 Apr-May;23(2-3):189-99. doi: 10.1016/j.ijdevneu.2004.11.001. PMID: 15749245

Therapy

Garey JD, Damkier P, Scialli AR, Lusskin S, Braddock SR, Chouchana L, Cleary B, Conover EA, Diav-Citrin O, Dragovich RS, Garcia-Bournissen F, Hodson K, Kennedy D, Lamm SH, Lavigne SA, Običan SG, Panchaud A, Perrotta K, Romeo AN, Shechtman S, Weber-Schoendorfer C
Birth Defects Res 2024 Aug;116(8):e2392. doi: 10.1002/bdr2.2392. PMID: 39189597
Georgieff MK
Am J Obstet Gynecol 2020 Oct;223(4):516-524. Epub 2020 Mar 14 doi: 10.1016/j.ajog.2020.03.006. PMID: 32184147Free PMC Article
Ito S
Clin Pharmacol Ther 2018 Oct;104(4):592-594. doi: 10.1002/cpt.1182. PMID: 30222188
Thapar A, Cooper M
Lancet 2016 Mar 19;387(10024):1240-50. Epub 2015 Sep 17 doi: 10.1016/S0140-6736(15)00238-X. PMID: 26386541
Abdolmaleky HM, Zhou JR, Thiagalingam S
Epigenomics 2015;7(3):427-49. doi: 10.2217/epi.14.85. PMID: 26077430

Prognosis

Wiggleton-Little J, Callender C
Kennedy Inst Ethics J 2023;33(1):21-54. doi: 10.1353/ken.2023.a899458. PMID: 38588127
Dawson G, Rieder AD, Johnson MH
Lancet Neurol 2023 Mar;22(3):244-254. Epub 2022 Nov 22 doi: 10.1016/S1474-4422(22)00407-0. PMID: 36427512Free PMC Article
Horien C, Floris DL, Greene AS, Noble S, Rolison M, Tejavibulya L, O'Connor D, McPartland JC, Scheinost D, Chawarska K, Lake EMR, Constable RT
Biol Psychiatry 2022 Oct 15;92(8):626-642. Epub 2022 Apr 25 doi: 10.1016/j.biopsych.2022.04.008. PMID: 35690495Free PMC Article
Baron-Cohen S
Ann N Y Acad Sci 2009 Mar;1156:68-80. doi: 10.1111/j.1749-6632.2009.04467.x. PMID: 19338503
Amaral DG, Schumann CM, Nordahl CW
Trends Neurosci 2008 Mar;31(3):137-45. Epub 2008 Feb 6 doi: 10.1016/j.tins.2007.12.005. PMID: 18258309

Clinical prediction guides

Wiggleton-Little J, Callender C
Kennedy Inst Ethics J 2023;33(1):21-54. doi: 10.1353/ken.2023.a899458. PMID: 38588127
Dawson G, Rieder AD, Johnson MH
Lancet Neurol 2023 Mar;22(3):244-254. Epub 2022 Nov 22 doi: 10.1016/S1474-4422(22)00407-0. PMID: 36427512Free PMC Article
Donovan AP, Basson MA
J Anat 2017 Jan;230(1):4-15. Epub 2016 Sep 12 doi: 10.1111/joa.12542. PMID: 27620360Free PMC Article
Baron-Cohen S
Ann N Y Acad Sci 2009 Mar;1156:68-80. doi: 10.1111/j.1749-6632.2009.04467.x. PMID: 19338503
Amaral DG, Schumann CM, Nordahl CW
Trends Neurosci 2008 Mar;31(3):137-45. Epub 2008 Feb 6 doi: 10.1016/j.tins.2007.12.005. PMID: 18258309

Recent systematic reviews

Zeidan J, Fombonne E, Scorah J, Ibrahim A, Durkin MS, Saxena S, Yusuf A, Shih A, Elsabbagh M
Autism Res 2022 May;15(5):778-790. Epub 2022 Mar 3 doi: 10.1002/aur.2696. PMID: 35238171Free PMC Article
Silva EAD Junior, Medeiros WMB, Torro N, Sousa JMM, Almeida IBCM, Costa FBD, Pontes KM, Nunes ELG, Rosa MDD, Albuquerque KLGD
Trends Psychiatry Psychother 2022 Jun 13;44:e20200149. doi: 10.47626/2237-6089-2020-0149. PMID: 34043900Free PMC Article
Schor NF, Bianchi DW
Pediatr Neurol 2021 Oct;123:67-76. Epub 2021 Aug 6 doi: 10.1016/j.pediatrneurol.2021.07.012. PMID: 34399111Free PMC Article
Kittel-Schneider S, Quednow BB, Leutritz AL, McNeill RV, Reif A
Neurosci Biobehav Rev 2021 May;124:63-77. Epub 2021 Jan 28 doi: 10.1016/j.neubiorev.2021.01.002. PMID: 33516734
Sayal K, Prasad V, Daley D, Ford T, Coghill D
Lancet Psychiatry 2018 Feb;5(2):175-186. Epub 2017 Oct 9 doi: 10.1016/S2215-0366(17)30167-0. PMID: 29033005

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