MCID: MRS004
MIFTS: 43

Marshall-Smith Syndrome

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases

Aliases & Classifications for Marshall-Smith Syndrome

MalaCards integrated aliases for Marshall-Smith Syndrome:

Name: Marshall-Smith Syndrome 53 12 49 55 71 36 28 13 14 69
Mrshss 53 71
Accelerated Skeletal Maturation-Facial Dysmorphism-Failure to Thrive Syndrome 55
Mss 71

Characteristics:

Orphanet epidemiological data:

55
marshall-smith syndrome
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation
early death


HPO:

31
marshall-smith syndrome:
Mortality/Aging death in childhood
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Marshall-Smith Syndrome

NIH Rare Diseases : 49 Marshall-Smith syndrome (MRSHSS) is a genetic disorder in which individuals typically have advanced bone age, difficulties gaining weight (failure to thrive), unique facial features, and intellectual disability. Other signs and symptoms of this condition may include eye abnormalities, breathing difficulties, and neurological issues. Individuals may also have heart defects, an increased amount of body hair (hirsutism), and flat feet (pes planus). MRSHSS is caused by mutations in the NFIX gene. Most individuals with MRSHSS are the first in their family with this condition and are said to have a spontaneous (de novo) mutation. Although there is no specific treatment or cure for MRSHSS, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options based on each person’s symptoms. Aggressive management of the early breathing and feeding problems may improve survival in individuals affected by this condition. Last updated: 6/14/2017

MalaCards based summary : Marshall-Smith Syndrome, also known as mrshss, is related to marinesco-sjogren syndrome and marshall syndrome, and has symptoms including hypertelorism, intellectual disability and failure to thrive. An important gene associated with Marshall-Smith Syndrome is NFIX (Nuclear Factor I X). Affiliated tissues include bone, eye and heart, and related phenotype is mortality/aging.

OMIM : 53 The Marshall-Smith syndrome is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., 2005). (602535)

UniProtKB/Swiss-Prot : 71 Marshall-Smith syndrome: A distinct malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia. Additional skeletal findings include long and thin tubular bones, broad middle phalanges with relatively narrow distal phalanges, and scoliosis.

Disease Ontology : 12 A syndrome that is characterized by advanced bone age, failure to thrive, respiratory problems, dysmorphic facial features, and variable mental retardation.

Related Diseases for Marshall-Smith Syndrome

Graphical network of the top 20 diseases related to Marshall-Smith Syndrome:



Diseases related to Marshall-Smith Syndrome

Symptoms & Phenotypes for Marshall-Smith Syndrome

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Ears:
low-set ears
deafness
overfolded helices

Growth Other:
failure to thrive

Abdomen External Features:
umbilical hernia
omphalocele

Respiratory Larynx:
laryngomalacia

Head And Neck Mouth:
glossoptosis
gum hypertrophy
everted lips

Cardiovascular Heart:
atrial septal defect

Respiratory Nasopharynx:
choanal atresia
obstructive sleep apnea
choanal stenosis

Neurologic Central Nervous System:
cerebral atrophy
macrogyria
hypotonia
mental retardation
absent corpus callosum
more
Head And Neck Teeth:
irregular dentition

Skeletal Skull:
prominent frontal bone
long cranium
underdeveloped mandibular rami

Growth Weight:
underweight for length

Skeletal:
accelerated skeletal maturation (bone age of 4 at birth)

Chest RibsSternum Clavicles And Scapulae:
pectus excavatum
short sternum
thick clavicles
large sternal ossification centers

Skeletal Spine:
scoliosis
odontoid hypoplasia
atlantoaxial subluxation

Head And Neck Nose:
short nose
anteverted nares
flat nasal bridge
upturned nose

Head And Neck Face:
prominent forehead
micrognathia
retrognathia
short philtrum
midface hypoplasia
more
Cardiovascular Vascular:
patent ductus arteriosus

Respiratory Lung:
apnea
pulmonary hypertension
aspiration pneumonia

Head And Neck Eyes:
synophrys
shallow orbits
prominent eyes
bushy eyebrows
bluish sclerae

Skin Nails Hair Hair:
hypertrichosis

Skeletal Limbs:
thin long bones

Growth Height:
accelerated linear growth

Respiratory Airways:
rudimentary epiglottis

Skeletal Hands:
wide proximal and middle phalanges
bullet-shaped middle phalanges
narrow distal phalanges
distal widening of metacarpals


Clinical features from OMIM:

602535

Human phenotypes related to Marshall-Smith Syndrome:

55 31 (show top 50) (show all 69)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 55 31 frequent (33%) Frequent (79-30%) HP:0000316
2 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
3 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
4 scoliosis 55 31 frequent (33%) Frequent (79-30%) HP:0002650
5 gingival overgrowth 55 31 occasional (7.5%) Occasional (29-5%) HP:0000212
6 bowing of the long bones 55 31 hallmark (90%) Very frequent (99-80%) HP:0006487
7 short nose 55 31 frequent (33%) Frequent (79-30%) HP:0003196
8 anteverted nares 55 31 hallmark (90%) Very frequent (99-80%) HP:0000463
9 optic atrophy 55 31 occasional (7.5%) Occasional (29-5%) HP:0000648
10 prominent forehead 55 31 hallmark (90%) Very frequent (99-80%) HP:0011220
11 retrognathia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000278
12 joint hyperflexibility 55 31 hallmark (90%) Very frequent (99-80%) HP:0005692
13 thin skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000963
14 generalized hirsutism 55 31 frequent (33%) Frequent (79-30%) HP:0002230
15 reduced bone mineral density 55 31 frequent (33%) Frequent (79-30%) HP:0004349
16 ventriculomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0002119
17 cerebellar hypoplasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001321
18 open mouth 55 31 frequent (33%) Frequent (79-30%) HP:0000194
19 conductive hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000405
20 protruding tongue 55 31 frequent (33%) Frequent (79-30%) HP:0010808
21 choanal atresia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000453
22 bruising susceptibility 55 31 frequent (33%) Frequent (79-30%) HP:0000978
23 proptosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000520
24 craniosynostosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001363
25 blue sclerae 55 31 frequent (33%) Frequent (79-30%) HP:0000592
26 accelerated skeletal maturation 55 31 hallmark (90%) Very frequent (99-80%) HP:0005616
27 abnormality of cardiovascular system morphology 55 31 occasional (7.5%) Occasional (29-5%) HP:0030680
28 slender long bone 55 31 hallmark (90%) Very frequent (99-80%) HP:0003100
29 increased susceptibility to fractures 55 31 frequent (33%) Frequent (79-30%) HP:0002659
30 malar flattening 31 HP:0000272
31 low-set ears 31 HP:0000369
32 pectus excavatum 31 HP:0000767
33 agenesis of corpus callosum 31 HP:0001274
34 frontal bossing 31 HP:0002007
35 hearing impairment 31 HP:0000365
36 depressed nasal bridge 31 HP:0005280
37 umbilical hernia 31 HP:0001537
38 thick eyebrow 31 HP:0000574
39 laryngomalacia 31 HP:0001601
40 glossoptosis 31 HP:0000162
41 pulmonary arterial hypertension 31 HP:0002092
42 patent ductus arteriosus 31 HP:0001643
43 short sternum 31 HP:0000879
44 atrial septal defect 31 HP:0001631
45 short philtrum 31 HP:0000322
46 overfolded helix 31 HP:0000396
47 obstructive sleep apnea 31 HP:0002870
48 midface retrusion 31 HP:0011800
49 short distal phalanx of finger 31 HP:0009882
50 synophrys 31 HP:0000664

UMLS symptoms related to Marshall-Smith Syndrome:


apnea

MGI Mouse Phenotypes related to Marshall-Smith Syndrome:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.23 CACNA1A F9 LRP2 NFIC NFIX NSD1

Drugs & Therapeutics for Marshall-Smith Syndrome

Search Clinical Trials , NIH Clinical Center for Marshall-Smith Syndrome

Genetic Tests for Marshall-Smith Syndrome

Genetic tests related to Marshall-Smith Syndrome:

# Genetic test Affiliating Genes
1 Marshall-Smith Syndrome 28 NFIX

Anatomical Context for Marshall-Smith Syndrome

MalaCards organs/tissues related to Marshall-Smith Syndrome:

38
Bone, Eye, Heart, Skin, Tongue, T Cells

Publications for Marshall-Smith Syndrome

Articles related to Marshall-Smith Syndrome:

(show all 40)
# Title Authors Year
1
Marshall-Smith syndrome: Novel pathogenic variant and previously unreported associations with precocious puberty and aortic root dilatation. ( 28442439 )
2017
2
Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes. ( 26200704 )
2015
3
Marshall-Smith syndrome. ( 25813678 )
2015
4
Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome. ( 24924640 )
2014
5
Neonatal Marshall-Smith syndrome. ( 24556605 )
2014
6
Surgical correction of severe kyphoscoliosis resulting in a neurological complication in Marshall-Smith syndrome. ( 23943225 )
2013
7
Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism. ( 21790824 )
2011
8
Anesthesia out of surgical area in a child with Marshall-Smith Syndrome. ( 21273971 )
2011
9
A pigmentary skin defect is a new finding in Marshall-Smith syndrome. ( 21739579 )
2011
10
Treatment of refractory hip pain with sodium hyaluronate (Hyalgan(c)) in a patient with the Marshall-Smith Syndrome: A case report. ( 20731866 )
2010
11
Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome. ( 20673863 )
2010
12
Maxillomandibular distraction osteogenesis for Marshall-Smith syndrome. ( 20303330 )
2010
13
Phenotype and natural history in Marshall-Smith syndrome. ( 20949508 )
2010
14
Marshall-Smith syndrome and septo-optic dysplasia: an unreported association. ( 18627063 )
2008
15
Airway management and fiberoptic tracheal intubation via the laryngeal mask in a child with Marshall-Smith syndrome. ( 18315650 )
2008
16
Visual impairment and prolonged survival in a girl with Marshall-Smith syndrome. ( 16531739 )
2006
17
Marshall-Smith syndrome: natural history and evidence of an osteochondrodysplasia with connective tissue abnormalities. ( 16086394 )
2005
18
Marshall-Smith syndrome: Follow-up report of a four and a half year old male. ( 15054853 )
2004
19
Long-term follow-up of Marshall-Smith syndrome: report of one case. ( 15624371 )
2004
20
Marshall Smith syndrome and pregnancy. ( 14766465 )
2004
21
Osseous fragility in Marshall-Smith syndrome. ( 12749068 )
2003
22
Marshall-Smith syndrome in a Taiwanese patient with T-cell immunodeficiency. ( 12239732 )
2002
23
Long-term survival of a patient with Marshall-Smith syndrome. ( 12038204 )
2002
24
Case of partial trisomy 2q3 with clinical manifestations of Marshall-Smith syndrome. ( 10406675 )
1999
25
Marshall-Smith syndrome: case report of a newborn male and review of the literature. ( 10457856 )
1999
26
Neonatal death in Marshall-Smith syndrome. ( 9555581 )
1998
27
Difficult airway in a patient with Marshall-Smith syndrome. ( 9742541 )
1998
28
Anaesthetic management of a child with Marshall-Smith syndrome. ( 9717599 )
1998
29
Marshall-Smith syndrome: the expanding phenotype. ( 9350818 )
1997
30
The Marshall-Smith syndrome: a review of the laryngeal complications. ( 9208244 )
1997
31
Marshall-Smith syndrome: a distinct entity. ( 7883370 )
1994
32
Long survival of a patient with Marshall-Smith syndrome without respiratory complications. ( 8230168 )
1993
33
Cervicomedullary junction decompression in a case of Marshall-Smith syndrome. Case report. ( 2072173 )
1991
34
Marshall-Smith syndrome: new radiographic, clinical, and pathologic observations. ( 1909446 )
1991
35
The Marshall-Smith syndrome. ( 2079077 )
1990
36
Marshall-Smith syndrome: new aspects. ( 3205374 )
1988
37
Marshall-Smith syndrome: further delineation. ( 3051433 )
1988
38
Marshall-Smith syndrome: two case reports and a review of pulmonary manifestations. ( 6823423 )
1983
39
Marshall-Smith syndrome with large bifrontal diameter, broad distal femora, camptodactly, and without broad middle phalanges. ( 758435 )
1979
40
The syndrome of accelerated bone maturation in the newborn infant with dysmorphism and congenital malformations. (The so-called Marshall-Smith syndrome). ( 827733 )
1976

Variations for Marshall-Smith Syndrome

ClinVar genetic disease variations for Marshall-Smith Syndrome:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 NFIX NM_002501.3(NFIX): c.1008_1012delCTCTC (p.Ser337Glyfs) deletion Pathogenic rs398122871 GRCh37 Chromosome 19, 13189479: 13189483
2 NFIX NM_002501.3(NFIX): c.1048_1049insC (p.Leu351Alafs) insertion Pathogenic rs398122872 GRCh37 Chromosome 19, 13189520: 13189520
3 NFIX NM_002501.3(NFIX): c.1037_1038insT (p.Thr347Hisfs) insertion Pathogenic rs398122870 GRCh37 Chromosome 19, 13189508: 13189508
4 NFIX NM_002501.3(NFIX): c.1011_1012delTC (p.Gln338Glyfs) deletion Pathogenic rs398122869 GRCh37 Chromosome 19, 13189482: 13189483
5 NFIX NM_002501.3(NFIX): c.1243delG (p.Ala415Profs) deletion Pathogenic rs398122873 GRCh37 Chromosome 19, 13192658: 13192658
6 NFIX NM_002501.3(NFIX): c.994_995insT (p.Cys332Leufs) insertion Pathogenic rs398122874 GRCh37 Chromosome 19, 13189465: 13189465
7 NFIX NM_002501.3(NFIX): c.959_960insC (p.Ala321Glyfs) insertion Pathogenic rs398122875 GRCh37 Chromosome 19, 13189430: 13189430
8 NFIX NM_002501.3(NFIX): c.955+1G> A single nucleotide variant Pathogenic rs398122876 GRCh37 Chromosome 19, 13186486: 13186486
9 NFIX NM_002501.3(NFIX): c.955+1G> T single nucleotide variant Pathogenic rs398122876 GRCh37 Chromosome 19, 13186486: 13186486
10 NFIX NM_002501.3(NFIX): c.970_971delAA (p.Lys324Glufs) deletion Pathogenic rs797045738 GRCh37 Chromosome 19, 13189441: 13189442
11 NFIX NM_002501.3(NFIX): c.1080_1096del17 (p.Ser361Ilefs) deletion Pathogenic rs797045737 GRCh38 Chromosome 19, 13081681: 13081697
12 NFIX NM_002501.3(NFIX): c.927dup (p.Ser310Glnfs) duplication Pathogenic GRCh38 Chromosome 19, 13075643: 13075643
13 NFIX NC_000019.9: g.(?_13106632)_(13428155_?)del deletion Pathogenic GRCh37 Chromosome 19, 13106632: 13428155

Expression for Marshall-Smith Syndrome

Search GEO for disease gene expression data for Marshall-Smith Syndrome.

Pathways for Marshall-Smith Syndrome

GO Terms for Marshall-Smith Syndrome

Cellular components related to Marshall-Smith Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 dendrite GO:0030425 8.8 CACNA1A GNRH1 LRP2

Biological processes related to Marshall-Smith Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell death GO:0008219 8.62 CACNA1A OPTN

Sources for Marshall-Smith Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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