U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination(NEDMEHM)

MedGen UID:
1684142
Concept ID:
C5193057
Disease or Syndrome
Synonyms: NEDMEHM; NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, EPILEPSY, AND HYPOMYELINATION
 
Gene (location): MTHFS (15q25.1)
 
Monarch Initiative: MONDO:0032705
OMIM®: 618367
Orphanet: ORPHA597874

Definition

Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (NEDMEHM) is an autosomal recessive neurometabolic disorder characterized by these cardinal features. Patients also show an exaggerated startle reflex in early infancy (Rodan et al., 2018). [from OMIM]

Clinical features

From HPO
Short femur
MedGen UID:
87499
Concept ID:
C0345375
Congenital Abnormality
An abnormal shortening of the femur.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Short humerus
MedGen UID:
316907
Concept ID:
C1832117
Congenital Abnormality
Underdevelopment of the humerus.
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).
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
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.
Focal emotional seizure with laughing
MedGen UID:
78734
Concept ID:
C0270820
Disease or Syndrome
Focal emotional seizure with laughing (gelastic) is characterized by bursts of laughter or giggling, usually without appropriate related emotion of happiness, and described as 'mirthless'.
Tonic seizure
MedGen UID:
82855
Concept ID:
C0270844
Disease or Syndrome
A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.
Atonic seizure
MedGen UID:
78735
Concept ID:
C0270846
Disease or Syndrome
Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
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.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
Cerebral hypomyelination
MedGen UID:
383084
Concept ID:
C2677328
Finding
Reduced amount of myelin in the nervous system resulting from defective myelinogenesis in the white matter of the central nervous system.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
EEG with generalized slow activity
MedGen UID:
866862
Concept ID:
C4021217
Finding
Diffuse slowing of cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
Epiblepharon
MedGen UID:
488856
Concept ID:
C0344503
Congenital Abnormality
Redundant eyelid skin pressing the eyelashes against the cornea and/or conjunctiva.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Short umbilical cord
MedGen UID:
78620
Concept ID:
C0266786
Finding
Decreased length of the umbilical cord.
Nuchal cord
MedGen UID:
98024
Concept ID:
C0405124
Finding
A complication of pregnancy and delivery in which the umbilical cord wraps around the fetal neck once or multiple times.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination

Recent clinical studies

Etiology

Marafi D, Mitani T, Isikay S, Hertecant J, Almannai M, Manickam K, Abou Jamra R, El-Hattab AW, Rajah J, Fatih JM, Du H, Karaca E, Bayram Y, Punetha J, Rosenfeld JA, Jhangiani SN, Boerwinkle E, Akdemir ZC, Erdin S, Hunter JV, Gibbs RA, Pehlivan D, Posey JE, Lupski JR
Ann Clin Transl Neurol 2020 May;7(5):610-627. Epub 2020 Apr 14 doi: 10.1002/acn3.51003. PMID: 32286009Free PMC Article

Diagnosis

Kaur P, Neethukrishna K, Kumble A, Girisha KM, Shukla A
Am J Med Genet A 2019 May;179(5):857-861. Epub 2019 Feb 28 doi: 10.1002/ajmg.a.61103. PMID: 30816001
O'Brien A, Marshall CR, Blaser S, Ray PN, Yoon G
Eur J Hum Genet 2017 Jun;25(6):775-778. Epub 2017 Apr 5 doi: 10.1038/ejhg.2017.39. PMID: 28378817Free PMC Article
Kurata H, Terashima H, Nakashima M, Okazaki T, Matsumura W, Ohno K, Saito Y, Maegaki Y, Kubota M, Nanba E, Saitsu H, Matsumoto N, Kato M
Clin Genet 2016 Nov;90(5):437-444. Epub 2016 Jul 4 doi: 10.1111/cge.12813. PMID: 27246907

Therapy

Fichera M, Failla P, Saccuzzo L, Miceli M, Salvo E, Castiglia L, Galesi O, Grillo L, Calì F, Greco D, Amato C, Romano C, Elia M
Hum Genet 2019 Feb;138(2):187-198. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01972-3. PMID: 30656450
Pineda M, Vilaseca MA, Artuch R, Santos S, García González MM, Aracil A, Van Schaftingen E, Jaeken J
Dev Med Child Neurol 2000 Sep;42(9):629-33. doi: 10.1017/s0012162200001171. PMID: 11034457

Prognosis

Fichera M, Failla P, Saccuzzo L, Miceli M, Salvo E, Castiglia L, Galesi O, Grillo L, Calì F, Greco D, Amato C, Romano C, Elia M
Hum Genet 2019 Feb;138(2):187-198. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01972-3. PMID: 30656450

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
Marafi D, Mitani T, Isikay S, Hertecant J, Almannai M, Manickam K, Abou Jamra R, El-Hattab AW, Rajah J, Fatih JM, Du H, Karaca E, Bayram Y, Punetha J, Rosenfeld JA, Jhangiani SN, Boerwinkle E, Akdemir ZC, Erdin S, Hunter JV, Gibbs RA, Pehlivan D, Posey JE, Lupski JR
Ann Clin Transl Neurol 2020 May;7(5):610-627. Epub 2020 Apr 14 doi: 10.1002/acn3.51003. PMID: 32286009Free PMC Article
Fichera M, Failla P, Saccuzzo L, Miceli M, Salvo E, Castiglia L, Galesi O, Grillo L, Calì F, Greco D, Amato C, Romano C, Elia M
Hum Genet 2019 Feb;138(2):187-198. Epub 2019 Jan 17 doi: 10.1007/s00439-019-01972-3. PMID: 30656450
O'Brien A, Marshall CR, Blaser S, Ray PN, Yoon G
Eur J Hum Genet 2017 Jun;25(6):775-778. Epub 2017 Apr 5 doi: 10.1038/ejhg.2017.39. PMID: 28378817Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...