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Intellectual developmental disorder with neuropsychiatric features(IDDNPF)

MedGen UID:
1379216
Concept ID:
C4479636
Disease or Syndrome
Synonyms: IDDNPF; INTELLECTUAL DEVELOPMENTAL DISORDER WITH NEUROPSYCHIATRIC FEATURES
 
Gene (location): SLC45A1 (1p36.23)
 
Monarch Initiative: MONDO:0044322
OMIM®: 617532

Definition

Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present (summary by Srour et al., 2017). [from OMIM]

Clinical features

From HPO
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
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.
Atypical behavior
MedGen UID:
535345
Concept ID:
C0233514
Mental or Behavioral Dysfunction
Atypical behavior is an abnormality in a person's actions, which can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
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.
Obsessive-compulsive trait
MedGen UID:
322417
Concept ID:
C1834433
Finding
The presence of one or more obsessive-compulsive personality traits. Obsessions refer to persistent intrusive thoughts, and compulsions to intrusive behaviors, which the affected person experiences as involuntary, senseless, or repugnant.
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.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
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).

Professional guidelines

PubMed

D'Onofrio G, Accogli A, Severino M, Caliskan H, Kokotović T, Blazekovic A, Jercic KG, Markovic S, Zigman T, Goran K, Barišić N, Duranovic V, Ban A, Borovecki F, Ramadža DP, Barić I, Fazeli W, Herkenrath P, Marini C, Vittorini R, Gowda V, Bouman A, Rocca C, Alkhawaja IA, Murtaza BN, Rehman MMU, Al Alam C, Nader G, Mancardi MM, Giacomini T, Srivastava S, Alvi JR, Tomoum H, Matricardi S, Iacomino M, Riva A, Scala M, Madia F, Pistorio A, Salpietro V, Minetti C, Rivière JB, Srour M, Efthymiou S, Maroofian R, Houlden H, Vernes SC, Zara F, Striano P, Nagy V
Hum Genet 2023 Jul;142(7):909-925. Epub 2023 May 14 doi: 10.1007/s00439-023-02552-2. PMID: 37183190Free PMC Article
Albokhari D, Ng BG, Guberinic A, Daniel EJP, Engelhardt NM, Barone R, Fiumara A, Garavelli L, Trimarchi G, Wolfe L, Raymond KM, Morava E, He M, Freeze HH, Lam C, Edmondson AC
J Inherit Metab Dis 2022 Sep;45(5):969-980. Epub 2022 Jun 30 doi: 10.1002/jimd.12527. PMID: 35716054Free PMC Article
Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone PF, Axtell D, Blagowidow N, Cereda A, Costantino A, Cormier-Daire V, FitzPatrick D, Grados M, Groves L, Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis M, Mariani M, McCleery JP, Menke LA, Metrena A, O'Connor J, Oliver C, Pie J, Piening S, Potter CJ, Quaglio AL, Redeker E, Richman D, Rigamonti C, Shi A, Tümer Z, Van Balkom IDC, Hennekam RC
Nat Rev Genet 2018 Oct;19(10):649-666. doi: 10.1038/s41576-018-0031-0. PMID: 29995837Free PMC Article

Recent clinical studies

Etiology

Correa-da-Silva F, Fliers E, Swaab DF, Yi CX
J Neuroendocrinol 2021 Jul;33(7):e12994. Epub 2021 Jun 22 doi: 10.1111/jne.12994. PMID: 34156126Free PMC Article
Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone PF, Axtell D, Blagowidow N, Cereda A, Costantino A, Cormier-Daire V, FitzPatrick D, Grados M, Groves L, Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis M, Mariani M, McCleery JP, Menke LA, Metrena A, O'Connor J, Oliver C, Pie J, Piening S, Potter CJ, Quaglio AL, Redeker E, Richman D, Rigamonti C, Shi A, Tümer Z, Van Balkom IDC, Hennekam RC
Nat Rev Genet 2018 Oct;19(10):649-666. doi: 10.1038/s41576-018-0031-0. PMID: 29995837Free PMC Article
Butcher NJ, Boot E, Lang AE, Andrade D, Vorstman J, McDonald-McGinn D, Bassett AS
Am J Med Genet A 2018 Oct;176(10):2146-2159. Epub 2018 May 19 doi: 10.1002/ajmg.a.38708. PMID: 29777584Free PMC Article
Cox DM, Butler MG
Int J Mol Sci 2015 Feb 13;16(2):4068-82. doi: 10.3390/ijms16024068. PMID: 25689425Free PMC Article
Pandolfo M
Curr Opin Neurol 2013 Apr;26(2):137-45. doi: 10.1097/WCO.0b013e32835f19da. PMID: 23449174

Diagnosis

Mula M, Coleman H, Wilson SJ
Continuum (Minneap Minn) 2022 Apr 1;28(2):457-482. doi: 10.1212/CON.0000000000001123. PMID: 35393966
Shelkowitz E, Gantz MG, Ridenour TA, Scheimann AO, Strong T, Bohonowych J, Duis J
Am J Med Genet A 2022 May;188(5):1457-1463. Epub 2022 Jan 30 doi: 10.1002/ajmg.a.62662. PMID: 35098642
Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone PF, Axtell D, Blagowidow N, Cereda A, Costantino A, Cormier-Daire V, FitzPatrick D, Grados M, Groves L, Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis M, Mariani M, McCleery JP, Menke LA, Metrena A, O'Connor J, Oliver C, Pie J, Piening S, Potter CJ, Quaglio AL, Redeker E, Richman D, Rigamonti C, Shi A, Tümer Z, Van Balkom IDC, Hennekam RC
Nat Rev Genet 2018 Oct;19(10):649-666. doi: 10.1038/s41576-018-0031-0. PMID: 29995837Free PMC Article
Ciaccio C, Fontana L, Milani D, Tabano S, Miozzo M, Esposito S
Ital J Pediatr 2017 Apr 19;43(1):39. doi: 10.1186/s13052-017-0355-y. PMID: 28420439Free PMC Article
Pandolfo M
Curr Opin Neurol 2013 Apr;26(2):137-45. doi: 10.1097/WCO.0b013e32835f19da. PMID: 23449174

Therapy

Cerulli Irelli E, Cocchi E, Ramantani G, Caraballo RH, Giuliano L, Yilmaz T, Morano A, Panagiotakaki E, Operto FF, Gonzalez Giraldez B, Silvennoinen K, Casciato S, Comajuan M, Balestrini S, Fortunato F, Coppola A, Di Gennaro G, Labate A, Sofia V, Kluger GJ, Kasteleijn-Nolst Trenité DGA, Gambardella A, Baykan B, Sisodiya SM, Arzimanoglou A, Striano P, Di Bonaventura C; EMA Study Group
Neurology 2022 May 3;98(18):e1865-e1876. Epub 2022 Mar 15 doi: 10.1212/WNL.0000000000200165. PMID: 35292555
Samanta D
Pediatr Neurol 2020 Apr;105:3-9. Epub 2019 Nov 30 doi: 10.1016/j.pediatrneurol.2019.10.009. PMID: 32057594
Boot E, Butcher NJ, Udow S, Marras C, Mok KY, Kaneko S, Barrett MJ, Prontera P, Berman BD, Masellis M, Dufournet B, Nguyen K, Charles P, Mutez E, Danaila T, Jacquette A, Colin O, Drapier S, Borg M, Fiksinski AM, Vergaelen E, Swillen A, Vogels A, Plate A, Perandones C, Gasser T, Clerinx K, Bourdain F, Mills K, Williams NM, Wood NW, Booij J, Lang AE, Bassett AS; International Research Group on 22q11.2DS-associated Parkinson's Disease
Neurology 2018 Jun 5;90(23):e2059-e2067. Epub 2018 May 11 doi: 10.1212/WNL.0000000000005660. PMID: 29752303Free PMC Article
Thomas RH, Zhang LM, Carvill GL, Archer JS, Heavin SB, Mandelstam SA, Craiu D, Berkovic SF, Gill DS, Mefford HC, Scheffer IE; EuroEPINOMICS RES Consortium
Neurology 2015 Mar 3;84(9):951-8. Epub 2015 Feb 11 doi: 10.1212/WNL.0000000000001305. PMID: 25672921Free PMC Article
Tsiouris JA, Brown WT
CNS Drugs 2004;18(11):687-703. doi: 10.2165/00023210-200418110-00001. PMID: 15330685

Prognosis

Mula M, Coleman H, Wilson SJ
Continuum (Minneap Minn) 2022 Apr 1;28(2):457-482. doi: 10.1212/CON.0000000000001123. PMID: 35393966
Cerulli Irelli E, Cocchi E, Ramantani G, Caraballo RH, Giuliano L, Yilmaz T, Morano A, Panagiotakaki E, Operto FF, Gonzalez Giraldez B, Silvennoinen K, Casciato S, Comajuan M, Balestrini S, Fortunato F, Coppola A, Di Gennaro G, Labate A, Sofia V, Kluger GJ, Kasteleijn-Nolst Trenité DGA, Gambardella A, Baykan B, Sisodiya SM, Arzimanoglou A, Striano P, Di Bonaventura C; EMA Study Group
Neurology 2022 May 3;98(18):e1865-e1876. Epub 2022 Mar 15 doi: 10.1212/WNL.0000000000200165. PMID: 35292555
Guo H, Zhang Q, Dai R, Yu B, Hoekzema K, Tan J, Tan S, Jia X, Chung WK, Hernan R, Alkuraya FS, Alsulaiman A, Al-Muhaizea MA, Lesca G, Pons L, Labalme A, Laux L, Bryant E, Brown NJ, Savva E, Ayres S, Eratne D, Peeters H, Bilan F, Letienne-Cejudo L, Gilbert-Dussardier B, Ruiz-Arana IL, Merlini JM, Boizot A, Bartoloni L, Santoni F, Karlowicz D, McDonald M, Wu H, Hu Z, Chen G, Ou J, Brasch-Andersen C, Fagerberg CR, Dreyer I, Chun-Hui Tsai A, Slegesky V, McGee RB, Daniels B, Sellars EA, Carpenter LA, Schaefer B, Sacoto MJG, Begtrup A, Schnur RE, Punj S, Wentzensen IM, Rhodes L, Pan Q, Bernier RA, Chen C, Eichler EE, Xia K
Am J Hum Genet 2020 Nov 5;107(5):963-976. doi: 10.1016/j.ajhg.2020.10.002. PMID: 33157009Free PMC Article
Ciaccio C, Fontana L, Milani D, Tabano S, Miozzo M, Esposito S
Ital J Pediatr 2017 Apr 19;43(1):39. doi: 10.1186/s13052-017-0355-y. PMID: 28420439Free PMC Article
Fraidakis MJ
Transl Psychiatry 2013 Sep 3;3(9):e302. doi: 10.1038/tp.2013.76. PMID: 24002088Free PMC Article

Clinical prediction guides

Meossi C, Carrer A, Ciaccio C, Estienne M, Silipigni R, Sciacca FL, Pantaleoni C, D'Arrigo S, Milani D
J Intellect Disabil Res 2023 Jul;67(7):679-689. Epub 2023 May 2 doi: 10.1111/jir.13038. PMID: 37129092
Mainka T, Fischer JF, Huebl J, Jung A, Lier D, Mosejova A, Skorvanek M, de Koning TJ, Kühn AA, Freisinger P, Ziagaki A, Ganos C
Parkinsonism Relat Disord 2021 Aug;89:167-175. Epub 2021 Jun 23 doi: 10.1016/j.parkreldis.2021.06.011. PMID: 34391119
Edwards SD, Schulze KV, Rosenfeld JA, Westerfield LE, Gerard A, Yuan B, Grigorenko EL, Posey JE, Bi W, Liu P
Am J Med Genet A 2021 May;185(5):1388-1398. Epub 2021 Feb 11 doi: 10.1002/ajmg.a.62104. PMID: 33576134
Guo H, Zhang Q, Dai R, Yu B, Hoekzema K, Tan J, Tan S, Jia X, Chung WK, Hernan R, Alkuraya FS, Alsulaiman A, Al-Muhaizea MA, Lesca G, Pons L, Labalme A, Laux L, Bryant E, Brown NJ, Savva E, Ayres S, Eratne D, Peeters H, Bilan F, Letienne-Cejudo L, Gilbert-Dussardier B, Ruiz-Arana IL, Merlini JM, Boizot A, Bartoloni L, Santoni F, Karlowicz D, McDonald M, Wu H, Hu Z, Chen G, Ou J, Brasch-Andersen C, Fagerberg CR, Dreyer I, Chun-Hui Tsai A, Slegesky V, McGee RB, Daniels B, Sellars EA, Carpenter LA, Schaefer B, Sacoto MJG, Begtrup A, Schnur RE, Punj S, Wentzensen IM, Rhodes L, Pan Q, Bernier RA, Chen C, Eichler EE, Xia K
Am J Hum Genet 2020 Nov 5;107(5):963-976. doi: 10.1016/j.ajhg.2020.10.002. PMID: 33157009Free PMC Article
Cox DM, Butler MG
Int J Mol Sci 2015 Feb 13;16(2):4068-82. doi: 10.3390/ijms16024068. PMID: 25689425Free PMC Article

Recent systematic reviews

Giani L, Michelini G, Nobile M, Ajmone PF, Vizziello PG, Scaini S
J Affect Disord 2022 Feb 15;299:636-643. Epub 2021 Dec 23 doi: 10.1016/j.jad.2021.12.099. PMID: 34953928
Kolevzon A, Delaby E, Berry-Kravis E, Buxbaum JD, Betancur C
Mol Autism 2019;10:50. Epub 2019 Dec 24 doi: 10.1186/s13229-019-0291-3. PMID: 31879555Free PMC Article
Kolc KL, Sadleir LG, Scheffer IE, Ivancevic A, Roberts R, Pham DH, Gecz J
Mol Psychiatry 2019 Feb;24(2):241-251. Epub 2018 Jun 11 doi: 10.1038/s41380-018-0066-9. PMID: 29892053Free PMC Article
Lee S, Rudd S, Gratten J, Visscher PM, Prins JB, Dawson PA
J Neurogenet 2018 Mar;32(1):6-14. Epub 2017 Dec 4 doi: 10.1080/01677063.2017.1404058. PMID: 29199528
Birch RC, Cornish KM, Hocking DR, Trollor JN
Neuropsychol Rev 2014 Dec;24(4):491-513. Epub 2014 May 15 doi: 10.1007/s11065-014-9262-9. PMID: 24828430

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