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Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive(NDHMSR)

MedGen UID:
1646665
Concept ID:
C4693325
Disease or Syndrome
Synonyms: NDHMSR; NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT HYPERKINETIC MOVEMENTS AND SEIZURES, AUTOSOMAL RECESSIVE
 
Gene (location): GRIN1 (9q34.3)
 
Monarch Initiative: MONDO:0060629
OMIM®: 617820

Disease characteristics

Excerpted from the GeneReview: GRIN1-Related Neurodevelopmental Disorder
GRIN1-related neurodevelopmental disorder (GRIN1-NDD) is characterized by mild-to-profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Other common manifestations are epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties, and behavior issues. A subset of individuals show a malformation of cortical development consisting of extensive and diffuse bilateral polymicrogyria. To date, 72 individuals with GRIN1-NDD have been reported. [from GeneReviews]
Authors:
Konrad Platzer  |  Johannes R Lemke   view full author information

Additional description

From OMIM
NDHMSR is an autosomal recessive neurodevelopmental disorder characterized by severely delayed psychomotor development, severe intellectual disability, and involuntary movements, including stereotypic movements, spasticity, and dystonia. Affected individuals are are usually unable to walk independently and have poor or absent speech. Some patients may have seizures (summary by Lemke et al., 2016).  http://www.omim.org/entry/617820

Clinical features

From HPO
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
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.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Involuntary movements
MedGen UID:
140884
Concept ID:
C0427086
Sign or Symptom
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.
Epileptic encephalopathy
MedGen UID:
452596
Concept ID:
C0543888
Disease or Syndrome
A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
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.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Delayed ability to sit
MedGen UID:
1368737
Concept ID:
C4476710
Finding
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Reduced social responsiveness
MedGen UID:
1841569
Concept ID:
C5826975
Finding
A reduced ability to participate in the back-and-forth flow of social interaction appropriate to culture and developmental level, which is normally characterized by an influence of the behavior of one person on the behavior of another person. This results in difficulty interacting with others through emotional, physical, or verbal communication.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

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

Bölte S, Neufeld J, Marschik PB, Williams ZJ, Gallagher L, Lai MC
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Thapar A, Cooper M
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Diagnosis

Bölte S, Neufeld J, Marschik PB, Williams ZJ, Gallagher L, Lai MC
Nat Rev Neurol 2023 Mar;19(3):136-159. Epub 2023 Feb 6 doi: 10.1038/s41582-023-00774-6. PMID: 36747038Free PMC Article
Morris-Rosendahl DJ, Crocq MA
Dialogues Clin Neurosci 2020 Mar;22(1):65-72. doi: 10.31887/DCNS.2020.22.1/macrocq. PMID: 32699506Free PMC Article
Thapar A, Cooper M, Rutter M
Lancet Psychiatry 2017 Apr;4(4):339-346. Epub 2016 Dec 13 doi: 10.1016/S2215-0366(16)30376-5. PMID: 27979720
Doernberg E, Hollander E
CNS Spectr 2016 Aug;21(4):295-9. Epub 2016 Jul 1 doi: 10.1017/S1092852916000262. PMID: 27364515
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

Therapy

Poudineh M, Parvin S, Omidali M, Nikzad F, Mohammadyari F, Sadeghi Poor Ranjbar F, Rasouli F, Nanbakhsh S, Olangian-Tehrani S
CNS Neurol Disord Drug Targets 2023;22(5):711-735. doi: 10.2174/1871527321666220517205813. PMID: 35585808
Weibel S, Menard O, Ionita A, Boumendjel M, Cabelguen C, Kraemer C, Micoulaud-Franchi JA, Bioulac S, Perroud N, Sauvaget A, Carton L, Gachet M, Lopez R
Encephale 2020 Feb;46(1):30-40. Epub 2019 Oct 11 doi: 10.1016/j.encep.2019.06.005. PMID: 31610922
Shamir R
Nestle Nutr Inst Workshop Ser 2016;86:67-76. Epub 2016 Jun 23 doi: 10.1159/000442724. PMID: 27336781
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
Margolis SS, Sell GL, Zbinden MA, Bird LM
Neurotherapeutics 2015 Jul;12(3):641-50. doi: 10.1007/s13311-015-0361-y. PMID: 26040994Free PMC Article

Prognosis

Ahrens AP, Hyötyläinen T, Petrone JR, Igelström K, George CD, Garrett TJ, Orešič M, Triplett EW, Ludvigsson J
Cell 2024 Apr 11;187(8):1853-1873.e15. Epub 2024 Apr 3 doi: 10.1016/j.cell.2024.02.035. PMID: 38574728
Hirvikoski T, Mittendorfer-Rutz E, Boman M, Larsson H, Lichtenstein P, Bölte S
Br J Psychiatry 2016 Mar;208(3):232-8. Epub 2015 Nov 5 doi: 10.1192/bjp.bp.114.160192. PMID: 26541693
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
Stoodley CJ
Cerebellum 2016 Feb;15(1):34-37. doi: 10.1007/s12311-015-0715-3. PMID: 26298473Free PMC Article
Kawicka A, Regulska-Ilow B
Rocz Panstw Zakl Hig 2013;64(1):1-12. PMID: 23789306

Clinical prediction guides

Ahrens AP, Hyötyläinen T, Petrone JR, Igelström K, George CD, Garrett TJ, Orešič M, Triplett EW, Ludvigsson J
Cell 2024 Apr 11;187(8):1853-1873.e15. Epub 2024 Apr 3 doi: 10.1016/j.cell.2024.02.035. PMID: 38574728
Morris-Rosendahl DJ, Crocq MA
Dialogues Clin Neurosci 2020 Mar;22(1):65-72. doi: 10.31887/DCNS.2020.22.1/macrocq. PMID: 32699506Free PMC Article
Turner TN, Wilfert AB, Bakken TE, Bernier RA, Pepper MR, Zhang Z, Torene RI, Retterer K, Eichler EE
Am J Hum Genet 2019 Dec 5;105(6):1274-1285. Epub 2019 Nov 27 doi: 10.1016/j.ajhg.2019.11.003. PMID: 31785789Free PMC Article
Perugi G, Hantouche E, Vannucchi G
Curr Neuropharmacol 2017 Apr;15(3):372-379. doi: 10.2174/1570159X14666160616120157. PMID: 28503108Free PMC Article
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Lancet Psychiatry 2017 Apr;4(4):339-346. Epub 2016 Dec 13 doi: 10.1016/S2215-0366(16)30376-5. PMID: 27979720

Recent systematic reviews

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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
Elliott SJ, Marshall D, Morley K, Uphoff E, Kumar M, Meader N
Cochrane Database Syst Rev 2021 Sep 3;9(9):CD013173. doi: 10.1002/14651858.CD013173.pub2. PMID: 34693989Free PMC Article
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
Lucas BR, Elliott EJ, Coggan S, Pinto RZ, Jirikowic T, McCoy SW, Latimer J
BMC Pediatr 2016 Nov 29;16(1):193. doi: 10.1186/s12887-016-0731-6. PMID: 27899082Free PMC Article

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