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Microcephaly, growth deficiency, seizures, and brain malformations(MIGSB)

MedGen UID:
1676229
Concept ID:
C5193042
Disease or Syndrome
Synonyms: MICROCEPHALY, GROWTH DEFICIENCY, SEIZURES, AND BRAIN MALFORMATIONS; MIGSB
 
Gene (location): WDR4 (21q22.3)
 
Monarch Initiative: MONDO:0032690
OMIM®: 618346

Definition

Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB) is a severe autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Additional features include optic atrophy, early-onset seizures, dysmorphic facial features, and brain malformations, such as partial agenesis of the corpus callosum and simplified gyration (summary by Shaheen et al., 2015). [from OMIM]

Clinical features

From HPO
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
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).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Large earlobe
MedGen UID:
334979
Concept ID:
C1844573
Finding
Increased volume of the earlobe, that is, abnormally prominent ear lobules.
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
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.
Partial agenesis of the corpus callosum
MedGen UID:
98127
Concept ID:
C0431368
Congenital Abnormality
A partial failure of the development of the corpus callosum.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
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.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
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.
Tented upper lip vermilion
MedGen UID:
326574
Concept ID:
C1839767
Finding
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Alveolar ridge overgrowth
MedGen UID:
400802
Concept ID:
C1865598
Finding
Increased width of the alveolar ridges.
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.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Professional guidelines

PubMed

Han J, Yang YD, He Y, Liu WJ, Zhen L, Pan M, Yang X, Zhang VW, Liao C, Li DZ
Prenat Diagn 2020 Apr;40(5):577-584. Epub 2020 Feb 10 doi: 10.1002/pd.5653. PMID: 31994750

Recent clinical studies

Etiology

Bowser LE, Young M, Wenger OK, Ammous Z, Brigatti KW, Carson VJ, Moser T, Deline J, Aoki K, Morlet T, Scott EM, Puffenberger EG, Robinson DL, Hendrickson C, Salvin J, Gottlieb S, Heaps AD, Tiemeyer M, Strauss KA
Mol Genet Metab 2019 Apr;126(4):475-488. Epub 2019 Jan 21 doi: 10.1016/j.ymgme.2019.01.013. PMID: 30691927
de Koning TJ
J Inherit Metab Dis 2017 Jul;40(4):609-620. Epub 2017 Jun 26 doi: 10.1007/s10545-017-0063-1. PMID: 28653176Free PMC Article
Prasad AN, Breen JC, Ampola MG, Rosman NP
J Child Neurol 1997 Aug;12(5):301-9. doi: 10.1177/088307389701200502. PMID: 9378897

Diagnosis

de Koning TJ
J Inherit Metab Dis 2017 Jul;40(4):609-620. Epub 2017 Jun 26 doi: 10.1007/s10545-017-0063-1. PMID: 28653176Free PMC Article
Meng L, Donti T, Xia F, Niu Z, Al Shamsi A, Hertecant J, Al-Jasmi F, Gibson JB, Nagakura H, Zhang J, He W, Eng C, Yang Y, Elsea SH
Am J Med Genet A 2017 Feb;173(2):460-470. Epub 2016 Nov 11 doi: 10.1002/ajmg.a.38049. PMID: 27860360
Webb EA, AlMutair A, Kelberman D, Bacchelli C, Chanudet E, Lescai F, Andoniadou CL, Banyan A, Alsawaid A, Alrifai MT, Alahmesh MA, Balwi M, Mousavy-Gharavy SN, Lukovic B, Burke D, McCabe MJ, Kasia T, Kleta R, Stupka E, Beales PL, Thompson DA, Chong WK, Alkuraya FS, Martinez-Barbera JP, Sowden JC, Dattani MT
Brain 2013 Oct;136(Pt 10):3096-105. Epub 2013 Sep 10 doi: 10.1093/brain/awt218. PMID: 24022475Free PMC Article
Maradin M, Fumić K, Hansikova H, Tesarova M, Wenchich L, Dorner S, Sarnavka V, Zeman J, Barić I
J Inherit Metab Dis 2006 Oct;29(5):683. Epub 2006 Aug 5 doi: 10.1007/s10545-006-0321-0. PMID: 16972175
Iannetti P, Schwartz CE, Dietz-Band J, Light E, Timmerman J, Chessa L
Am J Med Genet 1993 Aug 1;47(1):95-9. doi: 10.1002/ajmg.1320470120. PMID: 8368261

Therapy

Prasad AN, Breen JC, Ampola MG, Rosman NP
J Child Neurol 1997 Aug;12(5):301-9. doi: 10.1177/088307389701200502. PMID: 9378897

Prognosis

Himes RW, Chiou EH, Queliza K, Shouval DS, Somech R, Agarwal S, Jajoo K, Ziegler DS, Kratz CP, Huang J, Lucas TL, Myers KC, Nelson AS, DiNardo CD, Alter BP, Giri N, Khincha PP, McReynolds LJ, Dufour C, Pierri F, Goldman FD, Sherif Y, Savage SA, Miloh T, Bertuch AA
J Pediatr 2021 Mar;230:55-61.e4. Epub 2020 Sep 21 doi: 10.1016/j.jpeds.2020.09.038. PMID: 32971146
Woodbine L, Neal JA, Sasi NK, Shimada M, Deem K, Coleman H, Dobyns WB, Ogi T, Meek K, Davies EG, Jeggo PA
J Clin Invest 2013 Jul;123(7):2969-80. Epub 2013 Jun 3 doi: 10.1172/JCI67349. PMID: 23722905Free PMC Article
Prasad AN, Breen JC, Ampola MG, Rosman NP
J Child Neurol 1997 Aug;12(5):301-9. doi: 10.1177/088307389701200502. PMID: 9378897
Ishikawa T, Kawai K, Kanayama M, Wada Y
Pediatr Neurol 1987 Jan-Feb;3(1):37-9. doi: 10.1016/0887-8994(87)90053-1. PMID: 3508046

Clinical prediction guides

Staklinski SJ, Chang MC, Yu F, Collins Ruff K, Franz DN, Qian Z, Bloom LB, Merritt ME, McKenna R, Kilberg MS
J Biol Chem 2022 Sep;298(9):102385. Epub 2022 Aug 17 doi: 10.1016/j.jbc.2022.102385. PMID: 35985424Free PMC Article
Bowser LE, Young M, Wenger OK, Ammous Z, Brigatti KW, Carson VJ, Moser T, Deline J, Aoki K, Morlet T, Scott EM, Puffenberger EG, Robinson DL, Hendrickson C, Salvin J, Gottlieb S, Heaps AD, Tiemeyer M, Strauss KA
Mol Genet Metab 2019 Apr;126(4):475-488. Epub 2019 Jan 21 doi: 10.1016/j.ymgme.2019.01.013. PMID: 30691927
Vandekeere S, Dubois C, Kalucka J, Sullivan MR, García-Caballero M, Goveia J, Chen R, Diehl FF, Bar-Lev L, Souffreau J, Pircher A, Kumar S, Vinckier S, Hirabayashi Y, Furuya S, Schoonjans L, Eelen G, Ghesquière B, Keshet E, Li X, Vander Heiden MG, Dewerchin M, Carmeliet P
Cell Metab 2018 Oct 2;28(4):573-587.e13. Epub 2018 Jul 12 doi: 10.1016/j.cmet.2018.06.009. PMID: 30017355
de Koning TJ
J Inherit Metab Dis 2017 Jul;40(4):609-620. Epub 2017 Jun 26 doi: 10.1007/s10545-017-0063-1. PMID: 28653176Free PMC Article
Maradin M, Fumić K, Hansikova H, Tesarova M, Wenchich L, Dorner S, Sarnavka V, Zeman J, Barić I
J Inherit Metab Dis 2006 Oct;29(5):683. Epub 2006 Aug 5 doi: 10.1007/s10545-006-0321-0. PMID: 16972175

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