U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Neurodevelopmental disorder with speech impairment and dysmorphic facies(NEDSID)

MedGen UID:
1758434
Concept ID:
C5436699
Disease or Syndrome
Synonyms: NEDSID; NEURODEVELOPMENTAL DISORDER WITH SPEECH IMPAIRMENT AND DYSMORPHIC FACIES
 
Gene (location): SETD1A (16p11.2)
 
Monarch Initiative: MONDO:0033630
OMIM®: 619056

Definition

Neurodevelopmental disorder with speech impairment and dysmorphic facies (NEDSID) is characterized by developmental delay associated with mild to moderately impaired intellectual development or learning difficulties, behavioral or psychiatric abnormalities, and delayed speech and language acquisition. Additional features include dysmorphic facies, distal limb anomalies, gastrointestinal problems or feeding difficulties, and hypotonia. The phenotypic features and severity of the disorder are variable (summary by Kummeling et al., 2021). [from OMIM]

Clinical features

From HPO
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
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.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Aggressive behavior can denote verbal aggression, physical aggression against objects, physical aggression against people, and may also include aggression towards oneself.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tenseness, or panic, often in reaction to interpersonal stresses; worry about the negative effects of past unpleasant experiences and future negative possibilities; feeling fearful, apprehensive, or threatened by uncertainty; fears of falling apart or losing control.
Schizophrenia
MedGen UID:
48574
Concept ID:
C0036341
Mental or Behavioral Dysfunction
Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Sleep disturbance
MedGen UID:
52372
Concept ID:
C0037317
Sign or Symptom
An abnormality of sleep including such phenomena as 1) insomnia/hypersomnia, 2) non-restorative sleep, 3) sleep schedule disorder, 4) excessive daytime somnolence, 5) sleep apnea, and 6) restlessness.
Short attention span
MedGen UID:
82652
Concept ID:
C0262630
Finding
Reduced attention span characterized by distractibility and impulsivity but not necessarily satisfying the diagnostic criteria for attention deficit hyperactivity disorder.
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.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The ability of a joint to move beyond its normal range of motion.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
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).
Widely spaced teeth
MedGen UID:
337093
Concept ID:
C1844813
Finding
Increased spaces (diastemata) between most of the teeth in the same dental arch.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Everted upper lip vermilion
MedGen UID:
869272
Concept ID:
C4023698
Finding
Inner aspect of the upper lip vermilion (normally apposing the teeth) visible in a frontal view, i.e., the presence of an everted upper lip.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
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.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Professional guidelines

PubMed

Mishra S, Girisha KM, Shukla A
Clin Dysmorphol 2021 Jan;30(1):1-5. doi: 10.1097/MCD.0000000000000360. PMID: 33229923Free PMC Article
Fortnum H, Leighton P, Smith MD, Brown L, Jones M, Benton C, Marder E, Marshall A, Sutton K
Health Technol Assess 2014 Sep;18(60):1-147, v-vi. doi: 10.3310/hta18600. PMID: 25270051Free PMC Article

Recent clinical studies

Etiology

Zhang J, Gambin T, Yuan B, Szafranski P, Rosenfeld JA, Balwi MA, Alswaid A, Al-Gazali L, Shamsi AMA, Komara M, Ali BR, Roeder E, McAuley L, Roy DS, Manchester DK, Magoulas P, King LE, Hannig V, Bonneau D, Denommé-Pichon AS, Charif M, Besnard T, Bézieau S, Cogné B, Andrieux J, Zhu W, He W, Vetrini F, Ward PA, Cheung SW, Bi W, Eng CM, Lupski JR, Yang Y, Patel A, Lalani SR, Xia F, Stankiewicz P
Hum Genet 2017 Apr;136(4):377-386. Epub 2017 Mar 1 doi: 10.1007/s00439-017-1763-1. PMID: 28251352Free PMC Article
D'Souza D, D'Souza H, Johnson MH, Karmiloff-Smith A
Infant Behav Dev 2016 Aug;44:249-62. Epub 2016 Aug 4 doi: 10.1016/j.infbeh.2016.07.002. PMID: 27498221
Santen GW, Kriek M, van Attikum H
Epigenetics 2012 Nov;7(11):1219-24. Epub 2012 Sep 25 doi: 10.4161/epi.22299. PMID: 23010866Free PMC Article
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article
Richman LC
Cleft Palate Craniofac J 1997 Sep;34(5):390-5. doi: 10.1597/1545-1569_1997_034_0390_fasrtb_2.3.co_2. PMID: 9345605

Diagnosis

Glinton KE, Hurst ACE, Bowling KM, Cristian I, Haynes D, Adstamongkonkul D, Schnappauf O, Beck DB, Brewer C, Parikh AS, Shinde DN, Donaldson A, Brautbar A, Koene S, van Haeringen A, Piton A, Capri Y, Furlan M, Gardella E, Møller RS, van de Beek I, Zuurbier L, Lakeman P, Bayat A, Martinez J, Signer R, Torring PM, Engelund MB, Gripp KW, Amlie-Wolf L, Henderson LB, Midro AT, Tarasów E, Stasiewicz-Jarocka B, Moskal-Jasinska D, Vos P, Boschann F, Stoltenburg C, Puk O, Mero IL, Lossius K, Mignot C, Keren B, Acosta Guio JC, Briceño I, Gomez A, Yang Y, Stankiewicz P
Am J Med Genet A 2021 May;185(5):1366-1378. Epub 2021 Jan 31 doi: 10.1002/ajmg.a.62102. PMID: 33522091Free PMC Article
Curcio MR, Ferranti S, Lotti F, Grosso S
Neurol Sci 2021 Feb;42(2):727-729. Epub 2020 Oct 2 doi: 10.1007/s10072-020-04782-y. PMID: 33006724
Meyer R, Begemann M, Demuth S, Kraft F, Dey D, Schüler H, Busse S, Häusler M, Zerres K, Kurth I, Eggermann T, Elbracht M
Clin Genet 2020 Oct;98(4):408-412. Epub 2020 Aug 19 doi: 10.1111/cge.13819. PMID: 32720325
Wakeling EL
Arch Dis Child 2011 Dec;96(12):1156-61. Epub 2011 Feb 24 doi: 10.1136/adc.2010.190165. PMID: 21349887
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article

Therapy

Jinxiu L, Shuimei L, Ming X, Jonathan LC, Xiangju L, Wenyuan D
Medicine (Baltimore) 2020 Apr;99(16):e19813. doi: 10.1097/MD.0000000000019813. PMID: 32311999Free PMC Article
Fortnum H, Leighton P, Smith MD, Brown L, Jones M, Benton C, Marder E, Marshall A, Sutton K
Health Technol Assess 2014 Sep;18(60):1-147, v-vi. doi: 10.3310/hta18600. PMID: 25270051Free PMC Article
Strehle EM
Genet Couns 2011;22(2):173-85. PMID: 21848010
Elsabbagh M, Cohen H, Cohen M, Rosen S, Karmiloff-Smith A
J Intellect Disabil Res 2011 Jun;55(6):563-71. Epub 2011 Mar 15 doi: 10.1111/j.1365-2788.2011.01411.x. PMID: 21557785
Zackai EH, Mellman WJ, Neiderer B, Hanson JW
J Pediatr 1975 Aug;87(2):280-4. doi: 10.1016/s0022-3476(75)80603-2. PMID: 50427

Prognosis

Vasileiou G, Vergarajauregui S, Endele S, Popp B, Büttner C, Ekici AB, Gerard M, Bramswig NC, Albrecht B, Clayton-Smith J, Morton J, Tomkins S, Low K, Weber A, Wenzel M, Altmüller J, Li Y, Wollnik B, Hoganson G, Plona MR, Cho MT; Deciphering Developmental Disorders Study, Thiel CT, Lüdecke HJ, Strom TM, Calpena E, Wilkie AOM, Wieczorek D, Engel FB, Reis A
Am J Hum Genet 2018 Mar 1;102(3):468-479. Epub 2018 Feb 8 doi: 10.1016/j.ajhg.2018.01.014. PMID: 29429572Free PMC Article
Kleyner R, Malcolmson J, Tegay D, Ward K, Maughan A, Maughan G, Nelson L, Wang K, Robison R, Lyon GJ
Cold Spring Harb Mol Case Stud 2016 Nov;2(6):a001131. doi: 10.1101/mcs.a001131. PMID: 27900361Free PMC Article
Wakeling EL
Arch Dis Child 2011 Dec;96(12):1156-61. Epub 2011 Feb 24 doi: 10.1136/adc.2010.190165. PMID: 21349887
Turleau C
Orphanet J Rare Dis 2008 Feb 19;3:4. doi: 10.1186/1750-1172-3-4. PMID: 18284672Free PMC Article
Richman LC
Cleft Palate Craniofac J 1997 Sep;34(5):390-5. doi: 10.1597/1545-1569_1997_034_0390_fasrtb_2.3.co_2. PMID: 9345605

Clinical prediction guides

Zhao P, Meng Q, Wan C, Lei T, Zhang L, Zhang X, Tan L, Zhu H, He X
Neurogenetics 2023 Apr;24(2):129-136. Epub 2023 Feb 21 doi: 10.1007/s10048-023-00713-z. PMID: 36802310
Gokce-Samar Z, de Bellescize J, Arzimanoglou A, Putoux A, Chatron N, Lesca G, Portes VD
Eur J Med Genet 2022 Dec;65(12):104636. Epub 2022 Oct 7 doi: 10.1016/j.ejmg.2022.104636. PMID: 36216271
Meyer R, Begemann M, Demuth S, Kraft F, Dey D, Schüler H, Busse S, Häusler M, Zerres K, Kurth I, Eggermann T, Elbracht M
Clin Genet 2020 Oct;98(4):408-412. Epub 2020 Aug 19 doi: 10.1111/cge.13819. PMID: 32720325
Cusmano-Ozog K, Manning MA, Hoyme HE
Am J Med Genet C Semin Med Genet 2007 Nov 15;145C(4):393-8. doi: 10.1002/ajmg.c.30155. PMID: 17926345
Roccella M
Minerva Pediatr 1999 Jul-Aug;51(7-8):271-8. PMID: 10634060

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...