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Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities(NEDSHBA)

MedGen UID:
1708579
Concept ID:
C5394517
Disease or Syndrome
Synonyms: NEDSHBA; NEURODEVELOPMENTAL DISORDER WITH SEIZURES, HYPOTONIA, AND BRAIN IMAGING ABNORMALITIES
 
Gene (location): GRM7 (3p26.1)
 
Monarch Initiative: MONDO:0030063
OMIM®: 618922

Definition

Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, severe to profound intellectual impairment, early-onset refractory seizures, hypotonia, failure to thrive, and progressive microcephaly. Brain imaging shows cerebral atrophy, thin corpus callosum, and myelination defects. Death in childhood may occur (summary by Marafi et al., 2020). [from OMIM]

Clinical features

From HPO
Limb hypertonia
MedGen UID:
333083
Concept ID:
C1838391
Finding
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.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Nasogastric tube feeding in infancy
MedGen UID:
868930
Concept ID:
C4023343
Finding
Feeding problem necessitating nasogastric tube feeding.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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.
Self-mutilation
MedGen UID:
19925
Concept ID:
C0036601
Injury or Poisoning
Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die.
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Panhypopituitarism
MedGen UID:
69171
Concept ID:
C0242343
Disease or Syndrome
A pituitary functional deficit affecting all the anterior pituitary hormones (growth hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and prolactin).
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
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.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Reduced brain N-acetyl aspartate level by MRS
MedGen UID:
868367
Concept ID:
C4022761
Finding
A decrease in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS).
Elevated brain choline level by MRS
MedGen UID:
868369
Concept ID:
C4022763
Finding
An increase in the level of choline-containing compounds in the brain identified by magnetic resonance spectroscopy (MRS).
Interictal epileptiform activity
MedGen UID:
869073
Concept ID:
C4023491
Finding
Epileptiform activity refers to distinctive EEG waves or complexes distinguished from background activity found in in a proportion of human subjects with epilepsy, but which can also be found in subjects without seizures. Interictal epileptiform activity refers to such activity that occurs in the absence of a clinical or subclinical seizure.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Hippocampal atrophy
MedGen UID:
939097
Concept ID:
C4315130
Disease or Syndrome
Partial or complete wasting (loss) of hippocampus tissue that was once present.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Aspiration
MedGen UID:
751786
Concept ID:
C2712334
Finding
Inspiration of a foreign object into the airway.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Decreased response to growth hormone stimulation test
MedGen UID:
1784655
Concept ID:
C5539399
Finding
Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.
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.

Professional guidelines

PubMed

Oyama N, Vaneynde P, Reynhout S, Pao EM, Timms A, Fan X, Foss K, Derua R, Janssens V, Chung W, Mirzaa GM
J Med Genet 2023 May;60(5):511-522. Epub 2022 Oct 10 doi: 10.1136/jmg-2022-108713. PMID: 36216457
Ehtesham N, Mosallaei M, Beheshtian M, Khoshbakht S, Fadaee M, Vazehan R, Faraji Zonooz M, Karimzadeh P, Kahrizi K, Najmabadi H
Arch Iran Med 2022 Dec 1;25(12):788-797. doi: 10.34172/aim.2022.124. PMID: 37543906Free PMC Article
Kjaergaard S, Schwartz M, Skovby F
Arch Dis Child 2001 Sep;85(3):236-9. doi: 10.1136/adc.85.3.236. PMID: 11517108Free PMC Article

Recent clinical studies

Etiology

Khan TR, Leprince I, Messahel S, Minassian BA, Kayani S
Pediatr Neurol 2023 Mar;140:40-46. Epub 2022 Dec 7 doi: 10.1016/j.pediatrneurol.2022.12.002. PMID: 36599233
Ivanov I, Pacheva I, Yordanova R, Sotkova I, Galabova F, Gaberova K, Panova M, Gheneva I, Tsvetanova T, Noneva K, Dimitrova D, Markov S, Sapundzhiev N, Bichev S, Savov A
CNS Neurol Disord Drug Targets 2023;22(2):207-214. doi: 10.2174/1871527321666220221100704. PMID: 35189806
Ehtesham N, Mosallaei M, Beheshtian M, Khoshbakht S, Fadaee M, Vazehan R, Faraji Zonooz M, Karimzadeh P, Kahrizi K, Najmabadi H
Arch Iran Med 2022 Dec 1;25(12):788-797. doi: 10.34172/aim.2022.124. PMID: 37543906Free PMC Article
Budisteanu M, Papuc SM, Streata I, Cucu M, Pirvu A, Serban-Sosoi S, Erbescu A, Andrei E, Iliescu C, Ioana D, Severin E, Ioana M, Arghir A
Genes (Basel) 2021 Jul 1;12(7) doi: 10.3390/genes12071025. PMID: 34356041Free PMC Article
Vlaskamp DRM, Shaw BJ, Burgess R, Mei D, Montomoli M, Xie H, Myers CT, Bennett MF, XiangWei W, Williams D, Maas SM, Brooks AS, Mancini GMS, van de Laar IMBH, van Hagen JM, Ware TL, Webster RI, Malone S, Berkovic SF, Kalnins RM, Sicca F, Korenke GC, van Ravenswaaij-Arts CMA, Hildebrand MS, Mefford HC, Jiang Y, Guerrini R, Scheffer IE
Neurology 2019 Jan 8;92(2):e96-e107. Epub 2018 Dec 12 doi: 10.1212/WNL.0000000000006729. PMID: 30541864Free PMC Article

Diagnosis

Khan TR, Leprince I, Messahel S, Minassian BA, Kayani S
Pediatr Neurol 2023 Mar;140:40-46. Epub 2022 Dec 7 doi: 10.1016/j.pediatrneurol.2022.12.002. PMID: 36599233
Karaer K, Karaer D, Yüksel Z, Işikay S
Clin Dysmorphol 2022 Oct 1;31(4):167-173. Epub 2022 Jul 14 doi: 10.1097/MCD.0000000000000426. PMID: 36004946
Bolat H, Derin H, Ünsel-Bolat G
Cogn Behav Neurol 2022 Sep 1;35(3):221-226. doi: 10.1097/WNN.0000000000000309. PMID: 35766809
Poke G, King C, Muir A, de Valles-Ibáñez G, Germano M, Moura de Souza CF, Fung J, Chung B, Fung CW, Mignot C, Ilea A, Keren B, Vermersch AI, Davis S, Stanley T, Moharir M, Kannu P, Shao Z, Malerba N, Merla G, Mefford HC, Scheffer IE, Sadleir LG
Epilepsia 2019 Nov;60(11):e121-e127. Epub 2019 Oct 20 doi: 10.1111/epi.16372. PMID: 31631344
Ferretti A, Barresi S, Trivisano M, Ciolfi A, Dentici ML, Radio FC, Vigevano F, Tartaglia M, Specchio N
Am J Med Genet A 2019 Aug;179(8):1631-1636. Epub 2019 May 28 doi: 10.1002/ajmg.a.61206. PMID: 31136090

Therapy

Frank Y
Pediatr Neurol 2021 Sep;122:59-64. Epub 2021 Jun 16 doi: 10.1016/j.pediatrneurol.2021.06.002. PMID: 34325981
Vlaskamp DRM, Shaw BJ, Burgess R, Mei D, Montomoli M, Xie H, Myers CT, Bennett MF, XiangWei W, Williams D, Maas SM, Brooks AS, Mancini GMS, van de Laar IMBH, van Hagen JM, Ware TL, Webster RI, Malone S, Berkovic SF, Kalnins RM, Sicca F, Korenke GC, van Ravenswaaij-Arts CMA, Hildebrand MS, Mefford HC, Jiang Y, Guerrini R, Scheffer IE
Neurology 2019 Jan 8;92(2):e96-e107. Epub 2018 Dec 12 doi: 10.1212/WNL.0000000000006729. PMID: 30541864Free PMC Article
Sohail AH, Durrani MYK, Ibrahim SH, Humayun KN
J Coll Physicians Surg Pak 2018 Sep;28(9):S192-S194. doi: 10.29271/jcpsp.2018.09.S192. PMID: 30173695
Winstone AM, Stellitano LA, Verity CM
Dev Med Child Neurol 2017 Sep;59(9):965-972. Epub 2017 Jun 2 doi: 10.1111/dmcn.13476. PMID: 28574146
Camacho A, Núñez N, Dekomien G, Hernández-Laín A, de Aragón AM, Simón R
Eur J Paediatr Neurol 2015 Mar;19(2):243-7. Epub 2014 Dec 2 doi: 10.1016/j.ejpn.2014.11.005. PMID: 25500573

Prognosis

Poke G, King C, Muir A, de Valles-Ibáñez G, Germano M, Moura de Souza CF, Fung J, Chung B, Fung CW, Mignot C, Ilea A, Keren B, Vermersch AI, Davis S, Stanley T, Moharir M, Kannu P, Shao Z, Malerba N, Merla G, Mefford HC, Scheffer IE, Sadleir LG
Epilepsia 2019 Nov;60(11):e121-e127. Epub 2019 Oct 20 doi: 10.1111/epi.16372. PMID: 31631344
Zorlu P, Eksioglu AS, Ozkan M, Tos T, Senel S
Genet Couns 2014;25(3):299-303. PMID: 25365852
Kopyta I, Jamroz E, Kluczewska E, Sarecka-Hujar B
J Child Neurol 2014 Apr;29(4):442-9. Epub 2013 Mar 14 doi: 10.1177/0883073813478660. PMID: 23503883
Pearl PL, Gibson KM
Curr Opin Neurol 2004 Apr;17(2):107-13. doi: 10.1097/00019052-200404000-00005. PMID: 15021235
Thyen U, Aksu F, Bartsch O, Herb E
Neuropediatrics 1992 Dec;23(6):292-6. doi: 10.1055/s-2008-1071361. PMID: 1491747

Clinical prediction guides

Oyama N, Vaneynde P, Reynhout S, Pao EM, Timms A, Fan X, Foss K, Derua R, Janssens V, Chung W, Mirzaa GM
J Med Genet 2023 May;60(5):511-522. Epub 2022 Oct 10 doi: 10.1136/jmg-2022-108713. PMID: 36216457
Budisteanu M, Papuc SM, Streata I, Cucu M, Pirvu A, Serban-Sosoi S, Erbescu A, Andrei E, Iliescu C, Ioana D, Severin E, Ioana M, Arghir A
Genes (Basel) 2021 Jul 1;12(7) doi: 10.3390/genes12071025. PMID: 34356041Free 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
Poke G, King C, Muir A, de Valles-Ibáñez G, Germano M, Moura de Souza CF, Fung J, Chung B, Fung CW, Mignot C, Ilea A, Keren B, Vermersch AI, Davis S, Stanley T, Moharir M, Kannu P, Shao Z, Malerba N, Merla G, Mefford HC, Scheffer IE, Sadleir LG
Epilepsia 2019 Nov;60(11):e121-e127. Epub 2019 Oct 20 doi: 10.1111/epi.16372. PMID: 31631344
Kopyta I, Jamroz E, Kluczewska E, Sarecka-Hujar B
J Child Neurol 2014 Apr;29(4):442-9. Epub 2013 Mar 14 doi: 10.1177/0883073813478660. PMID: 23503883

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