RFMN
MCID: RFM001
MIFTS: 34

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 57 53 59 37 29 6 72
Spondyloepiphyseal Dysplasia, Retinal Dystrophy, and Antibody Deficiency 57
Spondyloepiphyseal Dysplasia-Retinal Dystrophy-Immunodeficiency Syndrome 59
Spondyloepiphseal Dysplasia, Retinal Dystrophy and Antibody Deficiency 53
Syndrome, Roifman 40
Rfmn 57

Characteristics:

Orphanet epidemiological data:

59
roifman syndrome
Inheritance: Autosomal recessive,X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
roifman syndrome:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 616651
KEGG 37 H01575
ICD10 via Orphanet 34 Q77.7
UMLS via Orphanet 73 C1846059
Orphanet 59 ORPHA353298
MedGen 42 C1846059
UMLS 72 C1846059

Summaries for Roifman Syndrome

KEGG : 37
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 : 57 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:

59 32 (show top 50) (show all 54)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 frequent (33%) Frequent (79-30%) HP:0000316
2 microcephaly 59 32 very rare (1%) Frequent (79-30%) HP:0000252
3 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
4 long philtrum 59 32 very rare (1%) Frequent (79-30%) HP:0000343
5 narrow nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0000446
6 generalized hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001290
7 epiphyseal dysplasia 59 32 frequent (33%) Frequent (79-30%) HP:0002656
8 intrauterine growth retardation 59 32 very rare (1%) Frequent (79-30%) HP:0001511
9 postnatal growth retardation 59 32 very rare (1%) Frequent (79-30%) HP:0008897
10 recurrent otitis media 59 32 frequent (33%) Frequent (79-30%) HP:0000403
11 short toe 59 32 frequent (33%) Frequent (79-30%) HP:0001831
12 hypogonadotrophic hypogonadism 59 32 frequent (33%) Frequent (79-30%) HP:0000044
13 decreased antibody level in blood 59 32 frequent (33%) Frequent (79-30%) HP:0004313
14 underdeveloped nasal alae 59 32 frequent (33%) Frequent (79-30%) HP:0000430
15 intellectual disability, moderate 59 32 frequent (33%) Frequent (79-30%) HP:0002342
16 clinodactyly of the 5th finger 59 32 very rare (1%) Frequent (79-30%) HP:0004209
17 brachydactyly 59 32 frequent (33%) Frequent (79-30%) HP:0001156
18 downturned corners of mouth 59 32 frequent (33%) Frequent (79-30%) HP:0002714
19 bilateral single transverse palmar creases 59 32 frequent (33%) Frequent (79-30%) HP:0007598
20 thin upper lip vermilion 59 32 very rare (1%) Frequent (79-30%) HP:0000219
21 recurrent pneumonia 59 32 frequent (33%) Frequent (79-30%) HP:0006532
22 eczema 59 32 very rare (1%) Frequent (79-30%) HP:0000964
23 long palpebral fissure 59 32 frequent (33%) Frequent (79-30%) HP:0000637
24 hip contracture 59 32 frequent (33%) Frequent (79-30%) HP:0003273
25 lymphadenopathy 59 32 frequent (33%) Frequent (79-30%) HP:0002716
26 hypoplasia of the corpus callosum 59 32 frequent (33%) Frequent (79-30%) HP:0002079
27 eosinophilia 59 32 frequent (33%) Frequent (79-30%) HP:0001880
28 hepatosplenomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0001433
29 retinal dystrophy 59 32 very rare (1%) Frequent (79-30%) HP:0000556
30 hyperconvex nail 59 32 frequent (33%) Frequent (79-30%) HP:0001795
31 biconvex vertebral bodies 59 32 frequent (33%) Frequent (79-30%) HP:0004625
32 spondyloepiphyseal dysplasia 59 32 frequent (33%) Frequent (79-30%) HP:0002655
33 irregular capital femoral epiphysis 59 32 frequent (33%) Frequent (79-30%) HP:0005041
34 broad femoral head 59 32 frequent (33%) Frequent (79-30%) HP:0008804
35 delayed proximal femoral epiphyseal ossification 59 32 frequent (33%) Frequent (79-30%) HP:0008828
36 prominent eyelashes 59 32 frequent (33%) Frequent (79-30%) HP:0011231
37 hippocampal atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0410170
38 noncompaction cardiomyopathy 59 32 very rare (1%) Very rare (<4-1%) HP:0012817
39 muscular hypotonia 32 very rare (1%) HP:0001252
40 global developmental delay 32 very rare (1%) HP:0001263
41 anteverted nares 32 very rare (1%) HP:0000463
42 ventricular septal defect 32 very rare (1%) HP:0001629
43 short metacarpal 32 very rare (1%) HP:0010049
44 single transverse palmar crease 32 very rare (1%) HP:0000954
45 narrow nose 32 very rare (1%) HP:0000460
46 short digit 32 very rare (1%) HP:0011927
47 splenomegaly 32 HP:0001744
48 hepatomegaly 32 HP:0002240
49 intellectual disability, mild 32 HP:0001256
50 downslanted palpebral fissures 32 HP:0000494

Symptoms via clinical synopsis from OMIM:

57
Abdomen Spleen:
splenomegaly

Head And Neck Face:
long philtrum

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

Skin Nails Hair Skin:
eczema

Hematology:
eosinophilia

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

Skeletal:
spondyloepiphyseal dysplasia

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

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

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 Spine:
irregular vertebral endplates
biconvex vertebrae

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:

41
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. 38 8 71
26522830 2015
2
Is Roifman syndrome an X-linked ciliopathy with humoral immunodeficiency? Evidence from 2 new cases. 38 8 71
21977988 2011
3
Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome. 8 71
10189087 1999
4
Partial agenesis of the corpus callosum, hippocampal atrophy, and stable intellectual disability associated with Roifman syndrome. 38 8
21910238 2011
5
The cognitive and behavioural phenotype of Roifman syndrome. 38 8
16901296 2006
6
Noncompaction of the myocardium associated with Roifman syndrome. 38 8
11293748 2001
7
Hypogonadotrophic hypogonadism in Roifman syndrome. 38 8
10905663 2000
8
Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. 71
21474760 2011
9
Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA. 71
21474761 2011
10
New insights into minor splicing-a transcriptomic analysis of cells derived from TALS patients. 38
31175170 2019
11
Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype. 38
30368667 2018
12
Extending the critical regions for mutations in the non-coding gene RNU4ATAC in another patient with Roifman Syndrome. 38
30455926 2018
13
Abnormal differentiation of B cells and megakaryocytes in patients with Roifman syndrome. 38
29391254 2018
14
The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome. 38
29265708 2018
15
Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes. 38
28623346 2017
16
A homozygous mutation in the stem II domain of RNU4ATAC causes typical Roifman syndrome. 38
29263834 2017
17
Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome. 38
27040866 2016
18
Primary immunodeficiencies associated with eosinophilia. 38
27222657 2016

Variations for Roifman Syndrome

ClinVar genetic disease variations for Roifman Syndrome:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 RNU4ATAC NM_015282.3(CLASP1): c.196-605C> T single nucleotide variant Pathogenic rs188343279 2:122288506-122288506 2:121530930-121530930
2 RNU4ATAC NM_015282.3(CLASP1): c.196-570C> T single nucleotide variant Pathogenic rs750325275 2:122288471-122288471 2:121530895-121530895
3 RNU4ATAC NR_023343.1(RNU4ATAC): n.13C> T single nucleotide variant Pathogenic rs559979281 2:122288468-122288468 2:121530892-121530892
4 RNU4ATAC NM_015282.3(CLASP1): c.196-591C> T single nucleotide variant Pathogenic rs756026847 2:122288492-122288492 2:121530916-121530916
5 RNU4ATAC NM_015282.3(CLASP1): c.196-562G> A single nucleotide variant Pathogenic rs370715569 2:122288463-122288463 2:121530887-121530887
6 RNU4ATAC NM_015282.3(CLASP1): c.196-672A> G single nucleotide variant Pathogenic rs863225423 2:122288573-122288573 2:121530997-121530997
7 RNU4ATAC NR_023343.1(RNU4ATAC): n.48G> A single nucleotide variant Likely pathogenic 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
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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