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Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures(NEDMIMS)

MedGen UID:
1823981
Concept ID:
C5774208
Disease or Syndrome
Synonym: NEDMIMS
 
Gene (location): CHKA (11q13.2)
 
Monarch Initiative: MONDO:0859282
OMIM®: 620023

Definition

Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (NEDMIMS) is an autosomal recessive disorder characterized by severe global developmental delay apparent from infancy, impaired intellectual development, progressive microcephaly, and early-onset seizures that may be refractory to treatment. Affected individuals have poor overall growth and may have various movement abnormalities, including hypo- and hypertonia. Behavioral problems may also be observed (Klockner et al., 2022). [from OMIM]

Clinical features

From HPO
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
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.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Sleep abnormality
MedGen UID:
52372
Concept ID:
C0037317
Finding
An abnormal pattern in the quality, quantity, or characteristics of sleep.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
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.
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.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Recent clinical studies

Etiology

Mohammadi NA, Ahring PK, Yu Liao VW, Chua HC, Ortiz de la Rosa S, Johannesen KM, Michaeli-Yossef Y, Vincent-Devulder A, Meridda C, Bruel AL, Rossi A, Patel C, Klepper J, Bonanni P, Minghetti S, Trivisano M, Specchio N, Amor D, Auvin S, Baer S, Meyer P, Milh M, Salpietro V, Maroofian R, Lemke JR, Weckhuysen S, Christophersen P, Rubboli G, Chebib M, Jensen AA, Absalom NL, Møller RS
EBioMedicine 2024 Aug;106:105236. Epub 2024 Jul 11 doi: 10.1016/j.ebiom.2024.105236. PMID: 38996765Free PMC Article
Januel L, Chatron N, Rivier-Ringenbach C, Cabet S, Labalme A, Sahin Y, Darvish H, Kruer M, Bakhtiari S, Sanlaville D, de Sainte Agathe JM, Lesca G
Eur J Med Genet 2024 Feb;67:104893. Epub 2023 Dec 8 doi: 10.1016/j.ejmg.2023.104893. PMID: 38070825
Justel M, Jou C, Sariego-Jamardo A, Juliá-Palacios NA, Ortez C, Poch ML, Hedrera-Fernandez A, Gomez-Martin H, Codina A, Dominguez-Carral J, Muxart J, Hernández-Laín A, Vila-Bedmar S, Zulaica M, Cancho-Candela R, Castro MDC, de la Osa-Langreo A, Peña-Valenceja A, Marcos-Vadillo E, Prieto-Matos P, Pascual-Pascual SI, López de Munain A, Camacho A, Estevez-Arias B, Musokhranova U, Olivella M, Oyarzábal A, Jimenez-Mallebrera C, Domínguez-González C, Nascimento A, García-Cazorla À, Natera-de Benito D
J Med Genet 2023 Oct;60(10):965-973. Epub 2023 May 16 doi: 10.1136/jmg-2022-109132. PMID: 37197784Free PMC Article
Manoochehri J, Goodarzi HR, Tabei SMB
J Genet 2022;101 PMID: 36226339
Sánchez-Albisua I, Frölich S, Barth PG, Steinlin M, Krägeloh-Mann I
Orphanet J Rare Dis 2014 May 5;9:70. doi: 10.1186/1750-1172-9-70. PMID: 24886362Free PMC Article

Diagnosis

Mohammadi NA, Ahring PK, Yu Liao VW, Chua HC, Ortiz de la Rosa S, Johannesen KM, Michaeli-Yossef Y, Vincent-Devulder A, Meridda C, Bruel AL, Rossi A, Patel C, Klepper J, Bonanni P, Minghetti S, Trivisano M, Specchio N, Amor D, Auvin S, Baer S, Meyer P, Milh M, Salpietro V, Maroofian R, Lemke JR, Weckhuysen S, Christophersen P, Rubboli G, Chebib M, Jensen AA, Absalom NL, Møller RS
EBioMedicine 2024 Aug;106:105236. Epub 2024 Jul 11 doi: 10.1016/j.ebiom.2024.105236. PMID: 38996765Free PMC Article
Kaya Özçora GD, Söbü E, Gümüş U
Neurol Res 2023 Mar;45(3):226-233. Epub 2023 Feb 2 doi: 10.1080/01616412.2023.2170917. PMID: 36731496
Andelman-Gur MM, Leventer RJ, Hujirat M, Ganos C, Yosovich K, Carmi N, Lev D, Nissenkorn A, Dobyns WB, Bhatia K, Lerman-Sagie T, Blumkin L
Am J Med Genet A 2020 Oct;182(10):2207-2213. Epub 2020 Aug 17 doi: 10.1002/ajmg.a.61795. PMID: 33001581
Sachdeva R, Donkers SJ, Kim SY
Clin Anat 2016 Jul;29(5):561-7. Epub 2015 Nov 17 doi: 10.1002/ca.22659. PMID: 26480021
Verrotti A, D'Egidio C, Agostinelli S, Gobbi G
Eur J Paediatr Neurol 2012 Jan;16(1):3-9. Epub 2011 Oct 1 doi: 10.1016/j.ejpn.2011.09.005. PMID: 21962875

Therapy

Copping NA, McTighe SM, Fink KD, Silverman JL
Neurotherapeutics 2021 Jul;18(3):1535-1547. Epub 2021 Sep 15 doi: 10.1007/s13311-021-01082-x. PMID: 34528170Free PMC Article
Suzuki-Muromoto S, Wakusawa K, Miyabayashi T, Sato R, Okubo Y, Endo W, Inui T, Togashi N, Kato A, Oba H, Nakashima M, Saitsu H, Matsumoto N, Haginoya K
J Hum Genet 2018 Jun;63(6):749-753. Epub 2018 Mar 19 doi: 10.1038/s10038-018-0432-0. PMID: 29556033
Friedman JR, Thiele EA, Wang D, Levine KB, Cloherty EK, Pfeifer HH, De Vivo DC, Carruthers A, Natowicz MR
Mov Disord 2006 Feb;21(2):241-5. doi: 10.1002/mds.20660. PMID: 16149086
Blau N, Bonafé L, Krägeloh-Mann I, Thöny B, Kierat L, Häusler M, Ramaekers V
Neurology 2003 Sep 9;61(5):642-7. doi: 10.1212/01.wnl.0000082726.08631.e7. PMID: 12963755

Prognosis

Mohammadi NA, Ahring PK, Yu Liao VW, Chua HC, Ortiz de la Rosa S, Johannesen KM, Michaeli-Yossef Y, Vincent-Devulder A, Meridda C, Bruel AL, Rossi A, Patel C, Klepper J, Bonanni P, Minghetti S, Trivisano M, Specchio N, Amor D, Auvin S, Baer S, Meyer P, Milh M, Salpietro V, Maroofian R, Lemke JR, Weckhuysen S, Christophersen P, Rubboli G, Chebib M, Jensen AA, Absalom NL, Møller RS
EBioMedicine 2024 Aug;106:105236. Epub 2024 Jul 11 doi: 10.1016/j.ebiom.2024.105236. PMID: 38996765Free PMC Article
Kaya Özçora GD, Söbü E, Gümüş U
Neurol Res 2023 Mar;45(3):226-233. Epub 2023 Feb 2 doi: 10.1080/01616412.2023.2170917. PMID: 36731496
Spagnoli C, Fusco C, Percesepe A, Leuzzi V, Pisani F
Int J Mol Sci 2021 Apr 18;22(8) doi: 10.3390/ijms22084202. PMID: 33919646Free PMC Article
Sachdeva R, Donkers SJ, Kim SY
Clin Anat 2016 Jul;29(5):561-7. Epub 2015 Nov 17 doi: 10.1002/ca.22659. PMID: 26480021
Klepper J, Leiendecker B
Dev Med Child Neurol 2007 Sep;49(9):707-16. doi: 10.1111/j.1469-8749.2007.00707.x. PMID: 17718830

Clinical prediction guides

Mohammadi NA, Ahring PK, Yu Liao VW, Chua HC, Ortiz de la Rosa S, Johannesen KM, Michaeli-Yossef Y, Vincent-Devulder A, Meridda C, Bruel AL, Rossi A, Patel C, Klepper J, Bonanni P, Minghetti S, Trivisano M, Specchio N, Amor D, Auvin S, Baer S, Meyer P, Milh M, Salpietro V, Maroofian R, Lemke JR, Weckhuysen S, Christophersen P, Rubboli G, Chebib M, Jensen AA, Absalom NL, Møller RS
EBioMedicine 2024 Aug;106:105236. Epub 2024 Jul 11 doi: 10.1016/j.ebiom.2024.105236. PMID: 38996765Free PMC Article
Kaiyrzhanov R, Rad A, Lin SJ, Bertoli-Avella A, Kallemeijn WW, Godwin A, Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Karimiani EG, Hempel M, Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi JR, Ganieva M, Fowler B, Aanicai R, Tayfun GA, Al Saman A, Alswaid A, Amiri N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Monajemi GB, Mohammadi P, Samie S, Banu SH, Pinto Basto J, Kortüm F, Bauer M, Bauer P, Beetz C, Garshasbi M, Issa AH, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D, Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW, Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M, Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R
Brain 2024 Apr 4;147(4):1436-1456. doi: 10.1093/brain/awad380. PMID: 37951597Free PMC Article
Justel M, Jou C, Sariego-Jamardo A, Juliá-Palacios NA, Ortez C, Poch ML, Hedrera-Fernandez A, Gomez-Martin H, Codina A, Dominguez-Carral J, Muxart J, Hernández-Laín A, Vila-Bedmar S, Zulaica M, Cancho-Candela R, Castro MDC, de la Osa-Langreo A, Peña-Valenceja A, Marcos-Vadillo E, Prieto-Matos P, Pascual-Pascual SI, López de Munain A, Camacho A, Estevez-Arias B, Musokhranova U, Olivella M, Oyarzábal A, Jimenez-Mallebrera C, Domínguez-González C, Nascimento A, García-Cazorla À, Natera-de Benito D
J Med Genet 2023 Oct;60(10):965-973. Epub 2023 May 16 doi: 10.1136/jmg-2022-109132. PMID: 37197784Free PMC Article
Andelman-Gur MM, Leventer RJ, Hujirat M, Ganos C, Yosovich K, Carmi N, Lev D, Nissenkorn A, Dobyns WB, Bhatia K, Lerman-Sagie T, Blumkin L
Am J Med Genet A 2020 Oct;182(10):2207-2213. Epub 2020 Aug 17 doi: 10.1002/ajmg.a.61795. PMID: 33001581
Gorman KM, Meyer E, Grozeva D, Spinelli E, McTague A, Sanchis-Juan A, Carss KJ, Bryant E, Reich A, Schneider AL, Pressler RM, Simpson MA, Debelle GD, Wassmer E, Morton J, Sieciechowicz D, Jan-Kamsteeg E, Paciorkowski AR, King MD, Cross JH, Poduri A, Mefford HC, Scheffer IE, Haack TB, McCullagh G; Deciphering Developmental Disorders Study; UK10K Consortium; NIHR BioResource, Millichap JJ, Carvill GL, Clayton-Smith J, Maher ER, Raymond FL, Kurian MA
Am J Hum Genet 2019 May 2;104(5):948-956. Epub 2019 Apr 11 doi: 10.1016/j.ajhg.2019.03.005. PMID: 30982612Free PMC Article

Recent systematic reviews

Spagnoli C, Fusco C, Percesepe A, Leuzzi V, Pisani F
Int J Mol Sci 2021 Apr 18;22(8) doi: 10.3390/ijms22084202. PMID: 33919646Free PMC Article

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