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Neurodevelopmental disorder with microcephaly and structural brain anomalies(NEDMIBA)

MedGen UID:
1677276
Concept ID:
C5193123
Disease or Syndrome
Synonyms: NEDMIBA; NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY AND STRUCTURAL BRAIN ANOMALIES
 
Gene (location): DYNC1I2 (2q31.1)
 
Monarch Initiative: MONDO:0032779
OMIM®: 618492

Clinical features

From HPO
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).
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).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
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 characterised 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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Absent septum pellucidum
MedGen UID:
96561
Concept ID:
C0431371
Congenital Abnormality
Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
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.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Hypernasal speech
MedGen UID:
107884
Concept ID:
C0566620
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
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).
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Recent clinical studies

Etiology

Prieto-Villalobos J, Alvear TF, Liberona A, Lucero CM, Martínez-Araya CJ, Balmazabal J, Inostroza CA, Ramírez G, Gómez GI, Orellana JA
Int J Mol Sci 2021 Sep 1;22(17) doi: 10.3390/ijms22179503. PMID: 34502412Free PMC Article
Malhotra A, Ziegler A, Shu L, Perrier R, Amlie-Wolf L, Wohler E, Lygia de Macena Sobreira N, Colin E, Vanderver A, Sherbini O, Stouffs K, Scalais E, Serretti A, Barth M, Navet B, Rollier P, Xi H, Wang H, Zhang H, Perry DL, Ferrarini A, Colombo R, Pepler A, Schneider A, Tomiwa K, Okamoto N, Matsumoto N, Miyake N, Taft R, Mao X, Bonneau D
J Med Genet 2021 Oct;58(10):712-716. Epub 2020 Aug 20 doi: 10.1136/jmedgenet-2020-107137. PMID: 32820033
Juric-Sekhar G, Hevner RF
Annu Rev Pathol 2019 Jan 24;14:293-318. doi: 10.1146/annurev-pathmechdis-012418-012927. PMID: 30677308Free PMC Article
Vianna P, Gomes JDA, Boquett JA, Fraga LR, Schuch JB, Vianna FSL, Schuler-Faccini L
Neuroimmunomodulation 2018;25(5-6):320-327. Epub 2019 Jan 10 doi: 10.1159/000495660. PMID: 30630174
Seltzer LE, Paciorkowski AR
Am J Med Genet C Semin Med Genet 2014 Jun;166C(2):140-55. Epub 2014 May 16 doi: 10.1002/ajmg.c.31400. PMID: 24839169

Diagnosis

Bijarnia-Mahay S, Somashekar PH, Kaur P, Kulshrestha S, Ramprasad VL, Murugan S, Sud S, Shukla A
J Hum Genet 2022 Mar;67(3):133-136. Epub 2021 Oct 8 doi: 10.1038/s10038-021-00981-3. PMID: 34621002Free PMC Article
Efthymiou S, Dutra-Clarke M, Maroofian R, Kaiyrzhanov R, Scala M, Reza Alvi J, Sultan T, Christoforou M, Tuyet Mai Nguyen T, Mankad K, Vona B, Rad A, Striano P, Salpietro V, Guillen Sacoto MJ, Zaki MS, Gleeson JG, Campeau PM, Russell BE, Houlden H
Epilepsia 2021 Feb;62(2):e35-e41. Epub 2021 Jan 7 doi: 10.1111/epi.16801. PMID: 33410539Free PMC Article
Daly T, Roberts A, Yang E, Mochida GH, Bodamer O
Am J Med Genet A 2020 Mar;182(3):441-445. Epub 2019 Dec 17 doi: 10.1002/ajmg.a.61454. PMID: 31846209
Huang L, Vanstone MR, Hartley T, Osmond M, Barrowman N, Allanson J, Baker L, Dabir TA, Dipple KM, Dobyns WB, Estrella J, Faghfoury H, Favaro FP, Goel H, Gregersen PA, Gripp KW, Grix A, Guion-Almeida ML, Harr MH, Hudson C, Hunter AG, Johnson J, Joss SK, Kimball A, Kini U, Kline AD, Lauzon J, Lildballe DL, López-González V, Martinezmoles J, Meldrum C, Mirzaa GM, Morel CF, Morton JE, Pyle LC, Quintero-Rivera F, Richer J, Scheuerle AE, Schönewolf-Greulich B, Shears DJ, Silver J, Smith AC, Temple IK; UCLA Clinical Genomics Center, van de Kamp JM, van Dijk FS, Vandersteen AM, White SM, Zackai EH, Zou R; Care4Rare Canada Consortium, Bulman DE, Boycott KM, Lines MA
Hum Mutat 2016 Feb;37(2):148-54. Epub 2015 Nov 19 doi: 10.1002/humu.22924. PMID: 26507355Free PMC Article
Seltzer LE, Paciorkowski AR
Am J Med Genet C Semin Med Genet 2014 Jun;166C(2):140-55. Epub 2014 May 16 doi: 10.1002/ajmg.c.31400. PMID: 24839169

Therapy

Basel-Vanagaite L, Smirin-Yosef P, Essakow JL, Tzur S, Lagovsky I, Maya I, Pasmanik-Chor M, Yeheskel A, Konen O, Orenstein N, Weisz Hubshman M, Drasinover V, Magal N, Peretz Amit G, Zalzstein Y, Zeharia A, Shohat M, Straussberg R, Monté D, Salmon-Divon M, Behar DM
Hum Genet 2015 Jun;134(6):577-87. Epub 2015 Mar 20 doi: 10.1007/s00439-015-1541-x. PMID: 25792360
Breuss M, Heng JI, Poirier K, Tian G, Jaglin XH, Qu Z, Braun A, Gstrein T, Ngo L, Haas M, Bahi-Buisson N, Moutard ML, Passemard S, Verloes A, Gressens P, Xie Y, Robson KJ, Rani DS, Thangaraj K, Clausen T, Chelly J, Cowan NJ, Keays DA
Cell Rep 2012 Dec 27;2(6):1554-62. Epub 2012 Dec 13 doi: 10.1016/j.celrep.2012.11.017. PMID: 23246003Free PMC Article
Opitz JM, de la Cruz F
Am J Med Genet 1994 May 1;50(4):326-38. doi: 10.1002/ajmg.1320500406. PMID: 7632194
Upfold JB, Smith MS
Med Hypotheses 1988 Sep;27(1):89-92. doi: 10.1016/0306-9877(88)90092-8. PMID: 3205209
Schaff-Blass E, Robertson GL, Rosenfield RL
J Pediatr 1983 May;102(5):703-8. doi: 10.1016/s0022-3476(83)80237-6. PMID: 6188820

Prognosis

Wu S, Jiang C, Li J, Zhang G, Shen Y, Wang J
BMC Med Genomics 2022 Jun 6;15(1):127. doi: 10.1186/s12920-022-01275-z. PMID: 35668446Free PMC Article
Cordelli DM, Di Pisa V, Fetta A, Garavelli L, Maltoni L, Soliani L, Ricci E
Genes (Basel) 2021 Jun 27;12(7) doi: 10.3390/genes12070982. PMID: 34199024Free PMC Article
Malhotra A, Ziegler A, Shu L, Perrier R, Amlie-Wolf L, Wohler E, Lygia de Macena Sobreira N, Colin E, Vanderver A, Sherbini O, Stouffs K, Scalais E, Serretti A, Barth M, Navet B, Rollier P, Xi H, Wang H, Zhang H, Perry DL, Ferrarini A, Colombo R, Pepler A, Schneider A, Tomiwa K, Okamoto N, Matsumoto N, Miyake N, Taft R, Mao X, Bonneau D
J Med Genet 2021 Oct;58(10):712-716. Epub 2020 Aug 20 doi: 10.1136/jmedgenet-2020-107137. PMID: 32820033
Bend R, Cohen L, Carter MT, Lyons MJ, Niyazov D, Mikati MA, Rojas SK, Person RE, Si Y, Wentzensen IM; Regeneron Genetics Center, Torti E, Lee JA, Boycott KM, Basel-Salmon L, Ferreira CR, Gonzaga-Jauregui C
Eur J Hum Genet 2020 Jan;28(1):76-87. Epub 2019 Aug 8 doi: 10.1038/s41431-019-0487-1. PMID: 31395947Free PMC Article
Lévy J, Coussement A, Dupont C, Guimiot F, Baumann C, Viot G, Passemard S, Capri Y, Drunat S, Verloes A, Pipiras E, Benzacken B, Dupont JM, Tabet AC
Am J Med Genet A 2017 Aug;173(8):2081-2087. Epub 2017 Jun 1 doi: 10.1002/ajmg.a.38302. PMID: 28573701

Clinical prediction guides

Guerrini R, Mei D, Kerti-Szigeti K, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB; DDD Study, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S; Undiagnosed Diseases Network, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R; ATP6V1A collaborators, Masuelli L, Conti V, Novarino G, Fassio A
Brain 2022 Aug 27;145(8):2687-2703. doi: 10.1093/brain/awac145. PMID: 35675510Free PMC Article
Prieto-Villalobos J, Alvear TF, Liberona A, Lucero CM, Martínez-Araya CJ, Balmazabal J, Inostroza CA, Ramírez G, Gómez GI, Orellana JA
Int J Mol Sci 2021 Sep 1;22(17) doi: 10.3390/ijms22179503. PMID: 34502412Free PMC Article
Andreu-Cervera A, Catala M, Schneider-Maunoury S
Neurobiol Dis 2021 Mar;150:105236. Epub 2020 Dec 28 doi: 10.1016/j.nbd.2020.105236. PMID: 33383187
Pringsheim M, Mitter D, Schröder S, Warthemann R, Plümacher K, Kluger G, Baethmann M, Bast T, Braun S, Büttel HM, Conover E, Courage C, Datta AN, Eger A, Grebe TA, Hasse-Wittmer A, Heruth M, Höft K, Kaindl AM, Karch S, Kautzky T, Korenke GC, Kruse B, Lutz RE, Omran H, Patzer S, Philippi H, Ramsey K, Rating T, Rieß A, Schimmel M, Westman R, Zech FM, Zirn B, Ulmke PA, Sokpor G, Tuoc T, Leha A, Staudt M, Brockmann K
Ann Clin Transl Neurol 2019 Apr;6(4):655-668. Epub 2019 Mar 3 doi: 10.1002/acn3.735. PMID: 31019990Free PMC Article
Vianna P, Gomes JDA, Boquett JA, Fraga LR, Schuch JB, Vianna FSL, Schuler-Faccini L
Neuroimmunomodulation 2018;25(5-6):320-327. Epub 2019 Jan 10 doi: 10.1159/000495660. PMID: 30630174

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