RMFSL
MCID: RGD002
MIFTS: 40

Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (RMFSL)

Categories: Genetic diseases, Muscle diseases

Aliases & Classifications for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

MalaCards integrated aliases for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:

Name: Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal 57 73 29 13 6 71
Rmfsl 57 73
Syndrome, Rigidity and Multifocal Seizure, Lethal Neonatal 39
Muscle Rigidity 44

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset at or soon after birth
death often in infancy or in childhood


HPO:

31
rigidity and multifocal seizure syndrome, lethal neonatal:
Onset and clinical course death in infancy progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

UniProtKB/Swiss-Prot : 73 Rigidity and multifocal seizure syndrome, lethal neonatal: A lethal, neonatal, neurologic disorder characterized by episodic jerking that is apparent in utero, lack of psychomotor development, axial and limb rigidity, frequent multifocal seizures, and dysautonomia. At birth, affected individuals have small heads, overlapping cranial sutures, small or absent fontanels, and depressed frontal bones. Infants show poorly responsive focal jerks of the tongue, face and arms in a nearly continuous sequence throughout life.

MalaCards based summary : Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal, also known as rmfsl, is related to malignant hyperthermia and central core disease of muscle, and has symptoms including clonus, apnea and myoclonic seizures. An important gene associated with Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal is BRAT1 (BRCA1 Associated ATM Activator 1). The drugs Remifentanil and Ketamine have been mentioned in the context of this disorder. Affiliated tissues include tongue, liver and cortex, and related phenotypes are optic atrophy and micrognathia

OMIM® : 57 Lethal neonatal rigidity and multifocal seizure syndrome is a severe autosomal recessive epileptic encephalopathy characterized by onset of rigidity and intractable seizures at or soon after birth. Affected infants achieve no developmental milestones and die within the first months or years of life (summary by Saitsu et al., 2014). (614498) (Updated 05-Mar-2021)

Related Diseases for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Diseases related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 94)
# Related Disease Score Top Affiliating Genes
1 malignant hyperthermia 11.2
2 central core disease of muscle 11.1
3 malignant hyperthermia 1 11.1
4 multiple system atrophy 1 11.1
5 basal ganglia calcification, idiopathic, 1 11.1
6 neurodegeneration with brain iron accumulation 1 11.1
7 epilepsy, pyridoxine-dependent 11.1
8 malignant hyperthermia 5 11.1
9 neuroleptic malignant syndrome 11.0
10 stiff-person syndrome 11.0
11 arthrogryposis, distal, type 2a 10.9
12 dystonia, dopa-responsive 10.9
13 malignant hyperthermia 2 10.9
14 malignant hyperthermia 3 10.9
15 spinal muscular atrophy with progressive myoclonic epilepsy 10.9
16 ceroid lipofuscinosis, neuronal, 3 10.9
17 deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome 10.9
18 hyperphosphatasia with mental retardation syndrome 1 10.9
19 epilepsy, myoclonic juvenile 10.9
20 lubs x-linked mental retardation syndrome 10.9
21 neurodegeneration with brain iron accumulation 5 10.9
22 ceroid lipofuscinosis, neuronal, 8 10.9
23 malignant hyperthermia 4 10.9
24 phosphoglycerate dehydrogenase deficiency 10.9
25 malignant hyperthermia 6 10.9
26 lissencephaly 1 10.9
27 salt and pepper developmental regression syndrome 10.9
28 striatal degeneration, autosomal dominant 1 10.9
29 ceroid lipofuscinosis, neuronal, 10 10.9
30 dystonia 16 10.9
31 parkinsonism-dystonia, infantile, 1 10.9
32 asparagine synthetase deficiency 10.9
33 myofibrillar myopathy 10 10.9
34 mitochondrial complex iv deficiency, nuclear type 8 10.9
35 basal ganglia calcification 10.9
36 hypermanganesemia with dystonia 10.9
37 neurodegeneration with brain iron accumulation 10.9
38 benign neonatal seizures 10.9
39 childhood absence epilepsy 10.9
40 unverricht-lundborg syndrome 10.9
41 striatonigral degeneration 10.9
42 biotin-thiamine-responsive basal ganglia disease 10.9
43 chd2-related neurodevelopmental disorders 10.9
44 mitochondrial membrane protein-associated neurodegeneration 10.9
45 prickle1-related progressive myoclonus epilepsy with ataxia 10.9
46 pura-related neurodevelopmental disorders 10.9
47 progressive myoclonus epilepsy, lafora type 10.9
48 scn8a-related epilepsy with encephalopathy 10.9
49 stac3 disorder 10.9
50 cdkl5 deficiency disorder 10.9

Graphical network of the top 20 diseases related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:



Diseases related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Symptoms & Phenotypes for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Human phenotypes related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 optic atrophy 31 occasional (7.5%) HP:0000648
2 micrognathia 31 occasional (7.5%) HP:0000347
3 delayed myelination 31 occasional (7.5%) HP:0012448
4 clonus 31 HP:0002169
5 global developmental delay 31 HP:0001263
6 inguinal hernia 31 HP:0000023
7 hypertonia 31 HP:0001276
8 flexion contracture 31 HP:0001371
9 apnea 31 HP:0002104
10 babinski sign 31 HP:0003487
11 rigidity 31 HP:0002063
12 muscular hypotonia of the trunk 31 HP:0008936
13 neuronal loss in central nervous system 31 HP:0002529
14 myoclonic spasms 31 HP:0003739
15 gliosis 31 HP:0002171
16 bradycardia 31 HP:0001662
17 abnormal autonomic nervous system physiology 31 HP:0012332
18 progressive microcephaly 31 HP:0000253
19 multifocal seizures 31 HP:0031165
20 generalized myoclonic seizure 31 HP:0002123

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
hyperreflexia
clonus
dysautonomia
hypertonia
multifocal seizures
more
Head And Neck Face:
micrognathia

Cardiovascular Heart:
bradycardia

Muscle Soft Tissue:
axial hypotonia

Head And Neck Eyes:
optic atrophy (1 family)

Prenatal Manifestations Movement:
episodic myoclonic spasms

Abdomen External Features:
inguinal hernia

Respiratory:
apnea

Skeletal:
joint contractures

Head And Neck Head:
microcephaly, progressive
small head (-1.5 to 2 sd)

Skeletal Skull:
small or absent fontanels
depressed frontal bones
overlapping cranial sutures

Clinical features from OMIM®:

614498 (Updated 05-Mar-2021)

UMLS symptoms related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:


clonus, apnea, myoclonic seizures

Drugs & Therapeutics for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Drugs for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Remifentanil Approved Phase 4 132875-61-7 60815
2
Ketamine Approved, Vet_approved Phase 4 6740-88-1 3821
3
Propofol Approved, Investigational, Vet_approved Phase 4 2078-54-8 4943
4 Anesthetics Phase 4
5 Neurotransmitter Agents Phase 4
6 Hypnotics and Sedatives Phase 4
7 Narcotics Phase 4
8 Analgesics, Opioid Phase 4
9 Anesthetics, Intravenous Phase 4
10 Anesthetics, Dissociative Phase 4
11 Excitatory Amino Acid Antagonists Phase 4
12 Analgesics Phase 4
13 Anesthetics, General Phase 4
14 Immunoglobulins Phase 1
15 gamma-Globulins Phase 1
16 Immunoglobulins, Intravenous Phase 1
17 Antibodies Phase 1
18 Rho(D) Immune Globulin Phase 1
19
Baclofen Approved 1134-47-0 2284
20 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Remifentanil-based Total Intravenous Anesthesia for Pediatric Rigid Bronchoscopy: Comparison of Propofol and Ketamine As Adjuvant Completed NCT01947114 Phase 4 Propofol;Ketamine;Remifentanil
2 The Efficacy of High-Dose Intravenous Immunoglobulin Therapy in Patients With Stiff-Man Syndrome: A Double-Blind, Placebo-Controlled Trial Completed NCT00001550 Phase 1 IVIg
3 the Evaluation of Diagnostic Value of Rigiscan Test (Nocturnal Penile Tumescence and Rigidity, NPTR) in Chinese Males Unknown status NCT02573805
4 Effects of Different Intensities of Passive Static Stretching on Flexibility, Neuromuscular and Functional Performance in Soccer Athletes: A Blinded, Randomized Controlled Trial. Unknown status NCT03150563
5 The Effect of Selective Laser Trabeculoplasty (SLT) on Ocular Rigidity Completed NCT01247831
6 Evaluation of Hepatic Rigidity by Ultrasonic Impulse Elastography in Liver Transplant Patients (SUPERSONIC) Completed NCT03174327
7 Long-term Surveillance of the MedStream Programmable Infusion System for the Intrathecal Infusion of Baclofen in the Treatment of Spasticity Terminated NCT01712087

Search NIH Clinical Center for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Cochrane evidence based reviews: muscle rigidity

Genetic Tests for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Genetic tests related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:

# Genetic test Affiliating Genes
1 Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal 29 BRAT1

Anatomical Context for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

MalaCards organs/tissues related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:

40
Tongue, Liver, Cortex, Cerebellum

Publications for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Articles related to Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:

(show all 13)
# Title Authors PMID Year
1
BRAT1 mutations present with a spectrum of clinical severity. 6 57 61
27282546 2016
2
Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes. 57 6
26535877 2015
3
Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation. 6 57
25500575 2015
4
Compound heterozygous BRAT1 mutations cause familial Ohtahara syndrome with hypertonia and microcephaly. 6 57
25319849 2014
5
Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. 57 6
23035047 2012
6
Genetic mapping and exome sequencing identify variants associated with five novel diseases. 6 57
22279524 2012
7
BRAT1 mutations are associated with infantile epileptic encephalopathy, mitochondrial dysfunction, and survival into childhood. 57
27282648 2016
8
An intronic variant in BRAT1 creates a cryptic splice site, causing epileptic encephalopathy without prominent rigidity. 61
33040300 2020
9
BRAT1 encephalopathy: a recessive cause of epilepsy of infancy with migrating focal seizures. 61
31868227 2020
10
Epilepsy of infancy with migrating focal seizures or rigidity and multifocal seizure syndrome, lethal neonatal? Different emphases on a severe phenotype. 61
31879938 2020
11
A novel pathogenic variant of BRAT1 gene causes rigidity and multifocal seizure syndrome, lethal neonatal. 61
32345087 2020
12
BRAT1 Mutation: The First Reported Case of Chinese Origin and Review of the Literature. 61
30346566 2018
13
Lethal neonatal rigidity and multifocal seizure syndrome with a new mutation in BRAT1. 61
28752061 2017

Variations for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

ClinVar genetic disease variations for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal:

6 (show top 50) (show all 391)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 BRAT1 NC_000007.14:g.(?_2538049)_(2539371_?)del Deletion Pathogenic 833357 7:2577683-2579005
2 BRAT1 NM_152743.4(BRAT1):c.398_405del (p.His133fs) Deletion Pathogenic 842737 7:2584568-2584575 7:2544934-2544941
3 BRAT1 NM_152743.4(BRAT1):c.1492del (p.Leu498fs) Deletion Pathogenic 848367 7:2579426-2579426 7:2539792-2539792
4 BRAT1 NM_152743.4(BRAT1):c.176T>C (p.Leu59Pro) SNV Pathogenic 180137 rs727505363 7:2587064-2587064 7:2547430-2547430
5 BRAT1 NM_152743.4(BRAT1):c.1177del (p.Ala393fs) Deletion Pathogenic 180139 rs727505365 7:2581076-2581076 7:2541442-2541442
6 BRAT1 NM_152743.4(BRAT1):c.1313_1314del (p.Gln438fs) Deletion Pathogenic 472936 rs749240175 7:2580939-2580940 7:2541305-2541306
7 BRAT1 NM_152743.4(BRAT1):c.803G>A (p.Arg268His) SNV Pathogenic 429928 rs1131691679 7:2583224-2583224 7:2543590-2543590
8 BRAT1 NM_152743.4(BRAT1):c.171del (p.Glu57fs) Deletion Pathogenic 559429 rs1554297097 7:2587069-2587069 7:2547435-2547435
9 BRAT1 NM_152743.4(BRAT1):c.1684C>T (p.Arg562Ter) SNV Pathogenic 661637 rs759216914 7:2578899-2578899 7:2539265-2539265
10 BRAT1 NM_152743.4(BRAT1):c.1576C>T (p.Gln526Ter) SNV Pathogenic 944680 7:2579199-2579199 7:2539565-2539565
11 BRAT1 NM_152743.4(BRAT1):c.105G>A (p.Trp35Ter) SNV Pathogenic 573854 rs1562596651 7:2593961-2593961 7:2554327-2554327
12 BRAT1 NM_152743.4(BRAT1):c.960_961TC[1] (p.Leu321fs) Microsatellite Pathogenic 180138 rs727505364 7:2581806-2581807 7:2542172-2542173
13 BRAT1 NM_152743.4(BRAT1):c.1543_1564delinsTC (p.Glu515fs) Indel Pathogenic 540176 rs1554293869 7:2579211-2579232 7:2539577-2539598
14 BRAT1 NM_152743.4(BRAT1):c.1013dup (p.Gly339fs) Duplication Pathogenic 647546 rs754341393 7:2581755-2581756 7:2542121-2542122
15 BRAT1 NM_152743.4(BRAT1):c.453_454insGAGAAGAT (p.Leu152fs) Insertion Pathogenic 180136 rs1554296088 7:2583573-2583574 7:2543939-2543940
16 BRAT1 NM_152743.4(BRAT1):c.1857G>A (p.Trp619Ter) SNV Pathogenic 202197 rs794729222 7:2578312-2578312 7:2538678-2538678
17 BRAT1 NM_152743.4(BRAT1):c.1499-1G>T SNV Pathogenic 872930
18 BRAT1 NM_152743.4(BRAT1):c.964C>T (p.Gln322Ter) SNV Pathogenic 434520 rs1554295159 7:2581805-2581805 7:2542171-2542171
19 BRAT1 NC_000007.14:g.(?_2544889)_(2554451_?)del Deletion Pathogenic 472924 7:2544889-2554451
20 BRAT1 NC_000007.14:g.(?_2554285)_(2554451_?)del Deletion Pathogenic 647953 7:2593919-2594085 7:2554285-2554451
21 BRAT1 NC_000007.14:g.(?_2554305)_(2554431_?)del Deletion Pathogenic 651803 7:2593939-2594065 7:2554305-2554431
22 BRAT1 NM_152743.4(BRAT1):c.638dup (p.Val214fs) Duplication Pathogenic 31199 rs730880324 7:2583388-2583389 7:2543754-2543755
23 BRAT1 NM_152743.4(BRAT1):c.294dup (p.Leu99fs) Duplication Pathogenic 279703 rs776913277 7:2584678-2584679 7:2545044-2545045
24 CLCN1 NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser) Indel Pathogenic 209139 rs797045032 7:143018813-143018814 7:143321720-143321721
25 BRAT1 NM_152743.4(BRAT1):c.419T>C (p.Leu140Pro) SNV Pathogenic 427101 rs1085307958 7:2584554-2584554 7:2544920-2544920
26 LOC106627981 NM_000157.4(GBA):c.1226A>G (p.Asn409Ser) SNV Likely pathogenic 4290 rs76763715 1:155205634-155205634 1:155235843-155235843
27 LOC106627981 NM_000157.4(GBA):c.1093G>A (p.Glu365Lys) SNV risk factor 199044 rs2230288 1:155206167-155206167 1:155236376-155236376
28 BRAT1 NM_152743.4(BRAT1):c.2125_2128del (p.Phe709fs) Deletion Likely pathogenic 372962 rs763527391 7:2578041-2578044 7:2538407-2538410
29 GCH1 NM_000161.3(GCH1):c.655C>T (p.Gln219Ter) SNV Likely pathogenic 523338 rs1555358382 14:55310833-55310833 14:54844115-54844115
30 BRAT1 NM_152743.4(BRAT1):c.1710del (p.Gln571fs) Deletion Likely pathogenic 817329 rs756489141 7:2578873-2578873 7:2539239-2539239
31 BRAT1 NM_152743.4(BRAT1):c.1371_1395+16del Deletion Likely pathogenic 654304 rs1224820591 7:2580597-2580637 7:2540963-2541003
32 BRAT1 NM_152743.4(BRAT1):c.283-2A>T SNV Likely pathogenic 650471 rs147005619 7:2584692-2584692 7:2545058-2545058
33 BRAT1 NM_152743.4(BRAT1):c.1395+2T>A SNV Likely pathogenic 848333 7:2580611-2580611 7:2540977-2540977
34 BRAT1 NC_000007.14:g.(?_2544889)_(2554451_?)dup Duplication Uncertain significance 830572 7:2584523-2594085
35 BRAT1 NC_000007.14:g.(?_2538049)_(2554451_?)dup Duplication Uncertain significance 830768 7:2577683-2594085
36 BRAT1 NM_152743.4(BRAT1):c.2323A>G (p.Met775Val) SNV Uncertain significance 842958 7:2577846-2577846 7:2538212-2538212
37 BRAT1 NM_152743.4(BRAT1):c.2051C>G (p.Pro684Arg) SNV Uncertain significance 845356 7:2578118-2578118 7:2538484-2538484
38 BRAT1 NM_152743.4(BRAT1):c.1688C>T (p.Ala563Val) SNV Uncertain significance 845683 7:2578895-2578895 7:2539261-2539261
39 BRAT1 NM_152743.4(BRAT1):c.2089C>T (p.His697Tyr) SNV Uncertain significance 846767 7:2578080-2578080 7:2538446-2538446
40 BRAT1 NM_152743.4(BRAT1):c.987G>A (p.Lys329=) SNV Uncertain significance 835385 7:2581782-2581782 7:2542148-2542148
41 BRAT1 NM_152743.4(BRAT1):c.577G>A (p.Ala193Thr) SNV Uncertain significance 836285 7:2583450-2583450 7:2543816-2543816
42 BRAT1 NM_152743.4(BRAT1):c.224_226del (p.Phe75del) Deletion Uncertain significance 837200 7:2587014-2587016 7:2547380-2547382
43 BRAT1 NM_152743.4(BRAT1):c.1395G>T (p.Thr465=) SNV Uncertain significance 838177 7:2580613-2580613 7:2540979-2540979
44 BRAT1 NM_152743.4(BRAT1):c.1405A>G (p.Lys469Glu) SNV Uncertain significance 838923 7:2579513-2579513 7:2539879-2539879
45 BRAT1 NM_152743.4(BRAT1):c.1795A>G (p.Ile599Val) SNV Uncertain significance 839149 7:2578374-2578374 7:2538740-2538740
46 BRAT1 NM_152743.4(BRAT1):c.1833G>A (p.Ala611=) SNV Uncertain significance 839831 7:2578336-2578336 7:2538702-2538702
47 BRAT1 NM_152743.4(BRAT1):c.1564G>A (p.Glu522Lys) SNV Uncertain significance 840355 7:2579211-2579211 7:2539577-2539577
48 BRAT1 NM_152743.4(BRAT1):c.1498+6G>A SNV Uncertain significance 848791 7:2579414-2579414 7:2539780-2539780
49 BRAT1 NM_152743.4(BRAT1):c.560C>T (p.Pro187Leu) SNV Uncertain significance 848825 7:2583467-2583467 7:2543833-2543833
50 BRAT1 NM_152743.4(BRAT1):c.104G>T (p.Trp35Leu) SNV Uncertain significance 849191 7:2593962-2593962 7:2554328-2554328

Expression for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Search GEO for disease gene expression data for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal.

Pathways for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

GO Terms for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

Sources for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
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44 MeSH
45 MESH via Orphanet
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49 NCI
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53 NINDS
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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