RMFSL
MCID: RGD002
MIFTS: 38

Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (RMFSL)

Categories: Genetic diseases, Neuronal diseases, Rare 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 75 29 13 6 73
Rmfsl 57 75
Lethal Neonatal Spasticity-Epileptic Encephalopathy Syndrome 59
Syndrome, Rigidity and Multifocal Seizure, Lethal Neonatal 40
Lethal Neonatal Rigidity-Multifocal Seizure Syndrome 59
Muscle Rigidity 44

Characteristics:

Orphanet epidemiological data:

59
lethal neonatal spasticity-epileptic encephalopathy syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: infantile;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
rigidity and multifocal seizure syndrome, lethal neonatal:
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

UniProtKB/Swiss-Prot : 75 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 stiff-person syndrome, 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). Affiliated tissues include bone, tongue and cerebellum, and related phenotypes are clonus and global developmental delay

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)

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 all 35)
# Related Disease Score Top Affiliating Genes
1 malignant hyperthermia 11.4
2 stiff-person syndrome 11.2
3 malignant hyperthermia 1 11.0
4 neurodegeneration with brain iron accumulation 1 11.0
5 epilepsy, pyridoxine-dependent 11.0
6 central core disease of muscle 10.9
7 multiple system atrophy 1 10.9
8 malignant hyperthermia 2 10.9
9 malignant hyperthermia 3 10.9
10 basal ganglia calcification, idiopathic, 1 10.9
11 lubs x-linked mental retardation syndrome 10.9
12 malignant hyperthermia 4 10.9
13 malignant hyperthermia 5 10.9
14 malignant hyperthermia 6 10.9
15 salt and pepper developmental regression syndrome 10.9
16 striatal degeneration, autosomal dominant 1 10.9
17 ceroid lipofuscinosis, neuronal, 10 10.9
18 epilepsy, idiopathic generalized 10 10.9
19 parkinsonism-dystonia, infantile, 1 10.9
20 neurodegeneration with brain iron accumulation 10.9
21 benign neonatal seizures 10.9
22 striatonigral degeneration 10.9
23 chd2 myoclonic encephalopathy 10.9
24 familial idiopathic basal ganglia calcification 10.9
25 neuroleptic malignant syndrome 10.0
26 malignant hyperthermia susceptibility 10.0
27 meningococcal meningitis 9.9
28 spindle cell hemangioma 9.9
29 meningitis 9.9
30 tremor 9.9
31 paramyotonia congenita of von eulenburg 9.8
32 arthrogryposis, distal, type 2a 9.8
33 essential tremor 9.8
34 myoclonus 9.8
35 serotonin syndrome 9.8

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

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
hyperreflexia
clonus
dysautonomia
hypertonia
extensor plantar responses
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

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

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 clonus 32 HP:0002169
2 global developmental delay 32 HP:0001263
3 optic atrophy 32 occasional (7.5%) HP:0000648
4 hypertonia 32 HP:0001276
5 flexion contracture 32 HP:0001371
6 micrognathia 32 occasional (7.5%) HP:0000347
7 generalized myoclonic seizures 32 HP:0002123
8 babinski sign 32 HP:0003487
9 apnea 32 HP:0002104
10 rigidity 32 HP:0002063
11 myoclonic spasms 32 HP:0003739
12 neuronal loss in central nervous system 32 HP:0002529
13 gliosis 32 HP:0002171
14 progressive microcephaly 32 HP:0000253
15 bradycardia 32 HP:0001662
16 abnormal autonomic nervous system physiology 32 HP:0012332
17 delayed myelination 32 occasional (7.5%) HP:0012448
18 multifocal seizures 32 HP:0031165

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

Search Clinical Trials , 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:

41
Bone, Tongue, Cerebellum, Cortex, Brain

Publications for Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal

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

(show all 22)
# Title Authors Year
1
Propofol Reduces Succinylcholine-induced Muscle Rigidity in a Patient with Paramyotonia Congenita. ( 28298805 )
2017
2
Impossible mask ventilation after an unusually low dose fentanyl-induced muscle rigidity in a patient with essential tremor: a case report and review of the literature. ( 25669008 )
2014
3
Temporal changes in serum creatine kinase concentration and degree of muscle rigidity in 24 patients with neuroleptic malignant syndrome. ( 23818785 )
2013
4
Elevated creatine kinase does not necessarily correspond temporally with onset of muscle rigidity in neuroleptic malignant syndrome: a report of two cases. ( 23271911 )
2012
5
Serotonin syndrome-muscle rigidity and confusion in the older adult. ( 22079646 )
2012
6
Masseter muscle rigidity: Atypical malignant hyperthermia presentation or isolated event? ( 21189861 )
2010
7
Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease. ( 18602099 )
2008
8
The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study. ( 17126974 )
2007
9
Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats. ( 12926542 )
2003
10
SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. ( 11400182 )
2001
11
Mental illness, muscle rigidity in tremors and renal failure. ( 11057788 )
2000
12
Raclopride and chlorpromazine, but not clozapine, increase muscle rigidity in the rat: relationship with D2 dopamine receptor occupancy. ( 10379524 )
1999
13
Neuroleptic malignant syndrome: two cases without muscle rigidity. ( 8839955 )
1996
14
Masseter muscle rigidity associated with glycine1306-to-alanine mutation in the adult muscle sodium channel alpha-subunit gene. ( 7741283 )
1995
15
The incidence of masseter muscle rigidity after succinylcholine in infants and children. ( 8069986 )
1994
16
Muscle rigidity in meningococcal meningitis. ( 8017607 )
1994
17
Masseter muscle rigidity and malignant hyperthermia susceptibility in pediatric patients. An update on management and diagnosis. ( 8010468 )
1994
18
Muscle rigidity in meningococcal meningitis. ( 8285338 )
1993
19
Muscle rigidity following halothane anesthesia in two patients with Freeman-Sheldon syndrome. ( 1519800 )
1992
20
Malignant hyperthermia susceptibility in adult patients with masseter muscle rigidity. ( 2295104 )
1990
21
Masseter muscle rigidity and malignant hyperthermia susceptibility. ( 3942303 )
1986
22
A patient with reflex myoclonus and muscle rigidity: "jerking stiff-man syndrome". ( 7217959 )
1980

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 359)
# Gene Variation Type Significance SNP ID Assembly Location
1 BRAT1 NM_152743.3(BRAT1): c.638dupA (p.Val214Glyfs) duplication Pathogenic rs730880324 GRCh37 Chromosome 7, 2583389: 2583389
2 BRAT1 NM_152743.3(BRAT1): c.638dupA (p.Val214Glyfs) duplication Pathogenic rs730880324 GRCh38 Chromosome 7, 2543755: 2543755
3 BRAT1 NM_152743.3(BRAT1): c.453_454insGAGAAGAT (p.Leu152Glufs) insertion Pathogenic rs727505362 GRCh38 Chromosome 7, 2543939: 2543940
4 BRAT1 NM_152743.3(BRAT1): c.453_454insGAGAAGAT (p.Leu152Glufs) insertion Pathogenic rs727505362 GRCh37 Chromosome 7, 2583573: 2583574
5 BRAT1 NM_152743.3(BRAT1): c.176T> C (p.Leu59Pro) single nucleotide variant Pathogenic rs727505363 GRCh37 Chromosome 7, 2587064: 2587064
6 BRAT1 NM_152743.3(BRAT1): c.176T> C (p.Leu59Pro) single nucleotide variant Pathogenic rs727505363 GRCh38 Chromosome 7, 2547430: 2547430
7 BRAT1 NM_152743.3(BRAT1): c.962_963delTC (p.Leu321Profs) deletion Pathogenic rs727505364 GRCh37 Chromosome 7, 2581806: 2581807
8 BRAT1 NM_152743.3(BRAT1): c.962_963delTC (p.Leu321Profs) deletion Pathogenic rs727505364 GRCh38 Chromosome 7, 2542172: 2542173
9 BRAT1 NM_152743.3(BRAT1): c.1177delG (p.Ala393Leufs) deletion Pathogenic rs727505365 GRCh37 Chromosome 7, 2581076: 2581076
10 BRAT1 NM_152743.3(BRAT1): c.1177delG (p.Ala393Leufs) deletion Pathogenic rs727505365 GRCh38 Chromosome 7, 2541442: 2541442
11 BRAT1 NM_152743.3(BRAT1): c.1857G> A (p.Trp619Ter) single nucleotide variant Pathogenic rs794729222 GRCh37 Chromosome 7, 2578312: 2578312
12 BRAT1 NM_152743.3(BRAT1): c.1857G> A (p.Trp619Ter) single nucleotide variant Pathogenic rs794729222 GRCh38 Chromosome 7, 2538678: 2538678
13 BRAT1 NM_152743.3(BRAT1): c.866G> C (p.Cys289Ser) single nucleotide variant Benign/Likely benign rs140451075 GRCh37 Chromosome 7, 2582895: 2582895
14 BRAT1 NM_152743.3(BRAT1): c.866G> C (p.Cys289Ser) single nucleotide variant Benign/Likely benign rs140451075 GRCh38 Chromosome 7, 2543261: 2543261
15 BRAT1 NM_152743.3(BRAT1): c.1825C> T (p.Arg609Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs886039312 GRCh37 Chromosome 7, 2578344: 2578344
16 BRAT1 NM_152743.3(BRAT1): c.1825C> T (p.Arg609Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs886039312 GRCh38 Chromosome 7, 2538710: 2538710
17 BRAT1 NM_152743.3(BRAT1): c.294dupA (p.Leu99Thrfs) duplication Pathogenic rs776913277 GRCh37 Chromosome 7, 2584679: 2584679
18 BRAT1 NM_152743.3(BRAT1): c.294dupA (p.Leu99Thrfs) duplication Pathogenic rs776913277 GRCh38 Chromosome 7, 2545045: 2545045
19 BRAT1 NM_152743.3(BRAT1): c.2125_2128delTTTG (p.Phe709Thrfs) deletion Conflicting interpretations of pathogenicity rs763527391 GRCh37 Chromosome 7, 2578041: 2578044
20 BRAT1 NM_152743.3(BRAT1): c.2125_2128delTTTG (p.Phe709Thrfs) deletion Conflicting interpretations of pathogenicity rs763527391 GRCh38 Chromosome 7, 2538407: 2538410
21 BRAT1 NM_152743.3(BRAT1): c.962T> G (p.Leu321Arg) single nucleotide variant Benign/Likely benign rs150942467 GRCh37 Chromosome 7, 2581807: 2581807
22 BRAT1 NM_152743.3(BRAT1): c.962T> G (p.Leu321Arg) single nucleotide variant Benign/Likely benign rs150942467 GRCh38 Chromosome 7, 2542173: 2542173
23 BRAT1 NM_152743.3(BRAT1): c.2041G> A (p.Glu681Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs145833100 GRCh37 Chromosome 7, 2578128: 2578128
24 BRAT1 NM_152743.3(BRAT1): c.2041G> A (p.Glu681Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs145833100 GRCh38 Chromosome 7, 2538494: 2538494
25 BRAT1 NM_152743.3(BRAT1): c.419T> C (p.Leu140Pro) single nucleotide variant Likely pathogenic rs1085307958 GRCh37 Chromosome 7, 2584554: 2584554
26 BRAT1 NM_152743.3(BRAT1): c.419T> C (p.Leu140Pro) single nucleotide variant Likely pathogenic rs1085307958 GRCh38 Chromosome 7, 2544920: 2544920
27 BRAT1 NM_152743.3(BRAT1): c.803G> A (p.Arg268His) single nucleotide variant Pathogenic/Likely pathogenic rs1131691679 GRCh37 Chromosome 7, 2583224: 2583224
28 BRAT1 NM_152743.3(BRAT1): c.803G> A (p.Arg268His) single nucleotide variant Pathogenic/Likely pathogenic rs1131691679 GRCh38 Chromosome 7, 2543590: 2543590
29 BRAT1 NM_152743.3(BRAT1): c.1884C> T (p.Ala628=) single nucleotide variant Benign rs142346283 GRCh38 Chromosome 7, 2538651: 2538651
30 BRAT1 NM_152743.3(BRAT1): c.1884C> T (p.Ala628=) single nucleotide variant Benign rs142346283 GRCh37 Chromosome 7, 2578285: 2578285
31 BRAT1 NM_152743.3(BRAT1): c.964C> T (p.Gln322Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 7, 2581805: 2581805
32 BRAT1 NM_152743.3(BRAT1): c.964C> T (p.Gln322Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 7, 2542171: 2542171
33 BRAT1 NM_152743.3(BRAT1): c.675C> T (p.Phe225=) single nucleotide variant Benign rs139443843 GRCh38 Chromosome 7, 2543718: 2543718
34 BRAT1 NM_152743.3(BRAT1): c.675C> T (p.Phe225=) single nucleotide variant Benign rs139443843 GRCh37 Chromosome 7, 2583352: 2583352
35 BRAT1 NM_152743.3(BRAT1): c.1879G> A (p.Ala627Thr) single nucleotide variant Uncertain significance rs750400556 GRCh37 Chromosome 7, 2578290: 2578290
36 BRAT1 NM_152743.3(BRAT1): c.1879G> A (p.Ala627Thr) single nucleotide variant Uncertain significance rs750400556 GRCh38 Chromosome 7, 2538656: 2538656
37 BRAT1 NM_152743.3(BRAT1): c.1867G> A (p.Gly623Ser) single nucleotide variant Benign/Likely benign rs77015302 GRCh37 Chromosome 7, 2578302: 2578302
38 BRAT1 NM_152743.3(BRAT1): c.1867G> A (p.Gly623Ser) single nucleotide variant Benign/Likely benign rs77015302 GRCh38 Chromosome 7, 2538668: 2538668
39 BRAT1 NM_152743.3(BRAT1): c.1135-8C> A single nucleotide variant Benign/Likely benign rs113613637 GRCh37 Chromosome 7, 2581126: 2581126
40 BRAT1 NM_152743.3(BRAT1): c.1135-8C> A single nucleotide variant Benign/Likely benign rs113613637 GRCh38 Chromosome 7, 2541492: 2541492
41 BRAT1 NM_152743.3(BRAT1): c.2353C> T (p.Arg785Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs61729932 GRCh37 Chromosome 7, 2577816: 2577816
42 BRAT1 NM_152743.3(BRAT1): c.2353C> T (p.Arg785Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs61729932 GRCh38 Chromosome 7, 2538182: 2538182
43 BRAT1 NM_152743.3(BRAT1): c.2209C> T (p.Arg737Trp) single nucleotide variant Benign rs60152725 GRCh38 Chromosome 7, 2538326: 2538326
44 BRAT1 NM_152743.3(BRAT1): c.2209C> T (p.Arg737Trp) single nucleotide variant Benign rs60152725 GRCh37 Chromosome 7, 2577960: 2577960
45 BRAT1 NM_152743.3(BRAT1): c.1931_1932delGAinsAG (p.Arg644Gln) indel Benign rs71531463 GRCh38 Chromosome 7, 2538603: 2538604
46 BRAT1 NM_152743.3(BRAT1): c.1931_1932delGAinsAG (p.Arg644Gln) indel Benign rs71531463 GRCh37 Chromosome 7, 2578237: 2578238
47 BRAT1 NM_152743.3(BRAT1): c.1828C> T (p.Arg610Trp) single nucleotide variant Uncertain significance rs61753094 GRCh37 Chromosome 7, 2578341: 2578341
48 BRAT1 NM_152743.3(BRAT1): c.1828C> T (p.Arg610Trp) single nucleotide variant Uncertain significance rs61753094 GRCh38 Chromosome 7, 2538707: 2538707
49 BRAT1 NM_152743.3(BRAT1): c.1206C> T (p.Asp402=) single nucleotide variant Benign rs7807895 GRCh37 Chromosome 7, 2581047: 2581047
50 BRAT1 NM_152743.3(BRAT1): c.1206C> T (p.Asp402=) single nucleotide variant Benign rs7807895 GRCh38 Chromosome 7, 2541413: 2541413

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

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