RFMN
MCID: RFM001
MIFTS: 35

Roifman Syndrome (RFMN)

Categories: Blood diseases, Bone diseases, Fetal diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Roifman Syndrome

MalaCards integrated aliases for Roifman Syndrome:

Name: Roifman Syndrome 56 52 58 36 29 6 71
Spondyloepiphyseal Dysplasia, Retinal Dystrophy, and Antibody Deficiency 56
Spondyloepiphyseal Dysplasia-Retinal Dystrophy-Immunodeficiency Syndrome 58
Spondyloepiphseal Dysplasia, Retinal Dystrophy and Antibody Deficiency 52
Syndrome, Roifman 39
Rfmn 56

Characteristics:

Orphanet epidemiological data:

58
roifman syndrome
Inheritance: Autosomal recessive,X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
roifman syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare bone diseases
Developmental anomalies during embryogenesis
Rare immunological diseases


Summaries for Roifman Syndrome

KEGG : 36 Roifman syndrome is a multi-system disorder with a physical phenotype that includes B-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy, and characteristic facial dysmorphism. Recently, whole-genome sequencing of Roifman syndrome patients have demonstrated that Roifman syndrome is caused by compound heterozygous single-nucleotide variants (SNVs) in the minor spliceosomal small nuclear RNA (snRNA) gene RNU4ATAC, which was already implicated in a severe congenital disorder, microcephalic osteodysplastic primordial dwarfism, type I (MOPD1) [DS:H00993]. Roifman syndrome is phenotypically distinct from MOPD1.

MalaCards based summary : Roifman Syndrome, also known as spondyloepiphyseal dysplasia, retinal dystrophy, and antibody deficiency, is related to roifman-chitayat syndrome and spondyloenchondrodysplasia with immune dysregulation. An important gene associated with Roifman Syndrome is RNU4ATAC (RNA, U4atac Small Nuclear (U12-Dependent Splicing)). Affiliated tissues include b cells, bone and t cells, and related phenotypes are hypertelorism and microcephaly

OMIM : 56 Roifman syndrome is a rare autosomal recessive disorder characterized by growth retardation, spondyloepiphyseal dysplasia, cognitive delay, facial dysmorphism, and antibody deficiency (summary by Merico et al., 2015). (616651)

Related Diseases for Roifman Syndrome

Graphical network of the top 20 diseases related to Roifman Syndrome:



Diseases related to Roifman Syndrome

Symptoms & Phenotypes for Roifman Syndrome

Human phenotypes related to Roifman Syndrome:

58 31 (show top 50) (show all 56)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000316
2 microcephaly 58 31 very rare (1%) Frequent (79-30%) HP:0000252
3 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
4 epiphyseal dysplasia 58 31 frequent (33%) Frequent (79-30%) HP:0002656
5 intrauterine growth retardation 58 31 very rare (1%) Frequent (79-30%) HP:0001511
6 postnatal growth retardation 58 31 very rare (1%) Frequent (79-30%) HP:0008897
7 recurrent otitis media 58 31 frequent (33%) Frequent (79-30%) HP:0000403
8 short toe 58 31 frequent (33%) Frequent (79-30%) HP:0001831
9 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
10 downturned corners of mouth 58 31 frequent (33%) Frequent (79-30%) HP:0002714
11 clinodactyly of the 5th finger 58 31 very rare (1%) Frequent (79-30%) HP:0004209
12 bilateral single transverse palmar creases 58 31 frequent (33%) Frequent (79-30%) HP:0007598
13 thin upper lip vermilion 58 31 very rare (1%) Frequent (79-30%) HP:0000219
14 long philtrum 58 31 very rare (1%) Frequent (79-30%) HP:0000343
15 intellectual disability, moderate 58 31 frequent (33%) Frequent (79-30%) HP:0002342
16 recurrent pneumonia 58 31 frequent (33%) Frequent (79-30%) HP:0006532
17 eczema 58 31 very rare (1%) Frequent (79-30%) HP:0000964
18 narrow nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000446
19 hip contracture 58 31 frequent (33%) Frequent (79-30%) HP:0003273
20 underdeveloped nasal alae 58 31 frequent (33%) Frequent (79-30%) HP:0000430
21 lymphadenopathy 58 31 frequent (33%) Frequent (79-30%) HP:0002716
22 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
23 eosinophilia 58 31 frequent (33%) Frequent (79-30%) HP:0001880
24 retinal dystrophy 58 31 very rare (1%) Frequent (79-30%) HP:0000556
25 generalized hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001290
26 hepatosplenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001433
27 hyperconvex nail 58 31 frequent (33%) Frequent (79-30%) HP:0001795
28 long palpebral fissure 58 31 frequent (33%) Frequent (79-30%) HP:0000637
29 biconvex vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0004625
30 spondyloepiphyseal dysplasia 58 31 frequent (33%) Frequent (79-30%) HP:0002655
31 irregular capital femoral epiphysis 58 31 frequent (33%) Frequent (79-30%) HP:0005041
32 broad femoral head 58 31 frequent (33%) Frequent (79-30%) HP:0008804
33 delayed proximal femoral epiphyseal ossification 58 31 frequent (33%) Frequent (79-30%) HP:0008828
34 prominent eyelashes 58 31 frequent (33%) Frequent (79-30%) HP:0011231
35 hippocampal atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0410170
36 hypogonadotropic hypogonadism 31 frequent (33%) HP:0000044
37 decreased circulating antibody level 31 frequent (33%) HP:0004313
38 noncompaction cardiomyopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0012817
39 global developmental delay 31 very rare (1%) HP:0001263
40 muscular hypotonia 31 very rare (1%) HP:0001252
41 anteverted nares 31 very rare (1%) HP:0000463
42 ventricular septal defect 31 very rare (1%) HP:0001629
43 short metacarpal 31 very rare (1%) HP:0010049
44 single transverse palmar crease 31 very rare (1%) HP:0000954
45 narrow nose 31 very rare (1%) HP:0000460
46 short digit 31 very rare (1%) HP:0011927
47 splenomegaly 31 HP:0001744
48 hepatomegaly 31 HP:0002240
49 intellectual disability, mild 31 HP:0001256
50 hypogonadotrophic hypogonadism 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Skeletal Hands:
brachydactyly
fifth finger clinodactyly
bilateral transverse palmar creases
small 3rd and 4th metacarpals

Head And Neck Face:
long philtrum

Skin Nails Hair Skin:
eczema

Hematology:
eosinophilia

Skeletal Spine:
irregular vertebral endplates
biconvex vertebrae

Head And Neck Nose:
narrow nose
hypoplastic alae nasi
upturned nose
tubular nose

Skin Nails Hair Nails:
hyperconvex nails

Head And Neck Head:
microcephaly (in some patients)

Prenatal Manifestations Delivery:
preterm delivery

Growth Other:
intrauterine growth restriction (iugr)

Skin Nails Hair Hair:
long, prominent eyelashes

Abdomen Liver:
hepatomegaly

Head And Neck Mouth:
downturned corners of mouth
thin upper lip

Respiratory Lung:
recurrent pneumonia

Immunology:
lymphadenopathy
recurrent infections (otitis media and bacterial pneumonia)
normal igg, iga, igm, ige levels
low specific antibody titers (e.g., tetanus, polio virus, mumps, rubella)
normal t-cell numbers
more
Head And Neck Eyes:
retinal dystrophy
downslanting palpebral fissures
long palpebral fissures
arteriolar attenuation
long, prominent eyelashes
more
Skeletal:
spondyloepiphyseal dysplasia

Neurologic Central Nervous System:
hypotonia
delayed developmental milestones
mental retardation, borderline-mild

Skeletal Pelvis:
hip flexion contractures
small, irregular proximal femoral epiphyses
broad femoral heads and necks
delayed ossification of proximal femoral epiphyses

Skeletal Feet:
short toes

Head And Neck Ears:
otitis media, recurrent

Growth Height:
short stature (short trunk)

Cardiovascular Heart:
noncompaction of the heart (rare)

Clinical features from OMIM:

616651

Drugs & Therapeutics for Roifman Syndrome

Search Clinical Trials , NIH Clinical Center for Roifman Syndrome

Genetic Tests for Roifman Syndrome

Genetic tests related to Roifman Syndrome:

# Genetic test Affiliating Genes
1 Roifman Syndrome 29 RNU4ATAC

Anatomical Context for Roifman Syndrome

MalaCards organs/tissues related to Roifman Syndrome:

40
B Cells, Bone, T Cells, Heart

Publications for Roifman Syndrome

Articles related to Roifman Syndrome:

(show all 18)
# Title Authors PMID Year
1
Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing. 56 61 6
26522830 2015
2
Is Roifman syndrome an X-linked ciliopathy with humoral immunodeficiency? Evidence from 2 new cases. 56 61 6
21977988 2011
3
Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome. 56 6
10189087 1999
4
Partial agenesis of the corpus callosum, hippocampal atrophy, and stable intellectual disability associated with Roifman syndrome. 61 56
21910238 2011
5
The cognitive and behavioural phenotype of Roifman syndrome. 56 61
16901296 2006
6
Noncompaction of the myocardium associated with Roifman syndrome. 56 61
11293748 2001
7
Hypogonadotrophic hypogonadism in Roifman syndrome. 61 56
10905663 2000
8
Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. 6
21474760 2011
9
Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA. 6
21474761 2011
10
New insights into minor splicing-a transcriptomic analysis of cells derived from TALS patients. 61
31175170 2019
11
Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype. 61
30368667 2018
12
Extending the critical regions for mutations in the non-coding gene RNU4ATAC in another patient with Roifman Syndrome. 61
30455926 2018
13
Abnormal differentiation of B cells and megakaryocytes in patients with Roifman syndrome. 61
29391254 2018
14
The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome. 61
29265708 2018
15
Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes. 61
28623346 2017
16
A homozygous mutation in the stem II domain of RNU4ATAC causes typical Roifman syndrome. 61
29263834 2017
17
Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome. 61
27040866 2016
18
Primary immunodeficiencies associated with eosinophilia. 61
27222657 2016

Variations for Roifman Syndrome

ClinVar genetic disease variations for Roifman Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RNU4ATAC NR_023343.1(RNU4ATAC):n.46G>ASNV Pathogenic 636959 2:122288501-122288501 2:121530925-121530925
2 RNU4ATAC NM_015282.3(CLASP1):c.196-605C>TSNV Pathogenic 30178 rs188343279 2:122288506-122288506 2:121530930-121530930
3 RNU4ATAC NR_023343.1(RNU4ATAC):n.13C>TSNV Pathogenic 218083 rs559979281 2:122288468-122288468 2:121530892-121530892
4 RNU4ATAC NM_015282.3(CLASP1):c.196-591C>TSNV Pathogenic 218084 rs756026847 2:122288492-122288492 2:121530916-121530916
5 RNU4ATAC NM_015282.3(CLASP1):c.196-562G>ASNV Pathogenic 218086 rs370715569 2:122288463-122288463 2:121530887-121530887
6 RNU4ATAC NM_015282.3(CLASP1):c.196-672A>GSNV Pathogenic 218087 rs863225423 2:122288573-122288573 2:121530997-121530997
7 RNU4ATAC NM_015282.3(CLASP1):c.196-570C>TSNV Pathogenic/Likely pathogenic 218082 rs750325275 2:122288471-122288471 2:121530895-121530895
8 RNU4ATAC NM_015282.3(CLASP1):c.196-670T>ASNV Likely pathogenic 812960 2:122288571-122288571 2:121530995-121530995
9 RNU4ATAC NR_023343.1(RNU4ATAC):n.116A>GSNV Likely pathogenic 870579 2:122288571-122288571 2:121530995-121530995
10 RNU4ATAC NR_023343.1(RNU4ATAC):n.48G>ASNV Likely pathogenic 218085 rs863225422 2:122288503-122288503 2:121530927-121530927

Expression for Roifman Syndrome

Search GEO for disease gene expression data for Roifman Syndrome.

Pathways for Roifman Syndrome

GO Terms for Roifman Syndrome

Sources for Roifman Syndrome

3 CDC
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68 SNOMED-CT via HPO
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70 Tocris
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72 UMLS via Orphanet
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