MCID: ART061
MIFTS: 34

Arthrogryposis, Distal, Type 2a

Categories: Genetic diseases, Fetal diseases, Rare diseases, Muscle diseases, Ear diseases

Aliases & Classifications for Arthrogryposis, Distal, Type 2a

MalaCards integrated aliases for Arthrogryposis, Distal, Type 2a:

Name: Arthrogryposis, Distal, Type 2a 54 24 13
Freeman-Sheldon Syndrome 71 29 69
Da2a 24 71
Whistling Face-Windmill Vane Hand Syndrome 71
Craniocarpotarsal Dysplasia 71
Craniocarpotarsal Dystrophy 71
Arthrogryposis, Distal, 2a 71
Fss 71

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
breech presentation
see also da2b , which is an allelic disorder
autosomal recessive form has also been described


HPO:

32
arthrogryposis, distal, type 2a:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 2a

OMIM : 54
Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120). (193700)

MalaCards based summary : Arthrogryposis, Distal, Type 2a, also known as freeman-sheldon syndrome, is related to distal arthrogryposis, and has symptoms including short stature, failure to thrive and scoliosis. An important gene associated with Arthrogryposis, Distal, Type 2a is MYH3 (Myosin Heavy Chain 3). The drugs Adenosine and Menthol have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and skeletal muscle.

Genetics Home Reference : 25 Freeman-Sheldon syndrome is a condition that primarily affects the face, hands, and feet. People with this disorder have a distinctive facial appearance including a small mouth (microstomia) with pursed lips, giving the appearance of a "whistling face." For this reason, the condition is sometimes called "whistling face syndrome."

UniProtKB/Swiss-Prot : 71 Arthrogryposis, distal, 2A: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2A is characterized by contractures of the hands and feet, oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice, puckered lips, and an H-shaped dimple of the chin.

Related Diseases for Arthrogryposis, Distal, Type 2a

Diseases in the Distal Arthrogryposis family:

Arthrogryposis, Distal, Type 10 Arthrogryposis, Distal, Type 5d
Arthrogryposis, Distal, Type 2b Arthrogryposis, Distal, Type 1b
Arthrogryposis, Distal, Type 2a Arthrogryposis, Distal, Type 8
Arthrogryposis, Distal, Type 5 Arthrogryposis, Distal, Type 3
Arthrogryposis, Distal, Type 6 Arthrogryposis, Distal, Type 4

Diseases related to Arthrogryposis, Distal, Type 2a via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 distal arthrogryposis 11.1

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 2a

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Eyes:
strabismus
ptosis
epicanthal folds
telecanthus
blepharophimosis
more
Head And Neck- Head:
microcephaly

Skeletal- Spine:
kyphoscoliosis
spina bifida occulta

Skeletal- Hands:
camptodactyly
ulnar deviation
cortical thumbs

Head And Neck- Nose:
small nose
broad nasal bridge
hypoplastic alae nasi

Head And Neck- Face:
long philtrum
flat face
full forehead
mask-like facies
h-shaped chin dimple
more
Skeletal- Feet:
vertical talus
equinovarus
contracted toes

Skeletal- Limbs:
shoulder contractures
knee contractures

Growth- Other:
postnatal growth deficiency
failure to thrive (infancy)

Muscle Soft Tissue:
[muscle]
mild muscle weakness
skeletal muscle biopsy shows fiber size variability
type 1 fiber type predominance
small type 1 fibers
more
Neurologic- Central Nervous System:
seizures
mental retardation (31%)

Head And Neck- Mouth:
small mouth
pursed lips

Skeletal- Pelvis:
hip contractures
hip dislocation

Head And Neck- Neck:
short neck

Genitourinary- External Genitalia Male:
inguinal hernia

Growth- Weight:
low birth weight

Voice:
nasal speech

Metabolic Features:
malignant hyperthermia
hyperpyrexia, usually associated with anesthesia

Skin Nails & Hair- Skin:
thickened skin over flexor surface of proximal phalanges


Clinical features from OMIM:

193700

Human phenotypes related to Arthrogryposis, Distal, Type 2a:

32 (show top 50) (show all 69)
id Description HPO Frequency HPO Source Accession
1 short stature 32 frequent (33%) HP:0004322
2 failure to thrive 32 hallmark (90%) HP:0001508
3 scoliosis 32 hallmark (90%) HP:0002650
4 strabismus 32 frequent (33%) HP:0000486
5 seizures 32 HP:0001250
6 ptosis 32 frequent (33%) HP:0000508
7 microcephaly 32 HP:0000252
8 prominent forehead 32 HP:0011220
9 hypertelorism 32 hallmark (90%) HP:0000316
10 hernia 32 occasional (7.5%) HP:0100790
11 kyphoscoliosis 32 HP:0002751
12 polyhydramnios 32 occasional (7.5%) HP:0001561
13 arthrogryposis multiplex congenita 32 HP:0002804
14 hip dislocation 32 HP:0002827
15 short nose 32 HP:0003196
16 muscle weakness 32 HP:0001324
17 cryptorchidism 32 frequent (33%) HP:0000028
18 camptodactyly 32 HP:0012385
19 talipes equinovarus 32 hallmark (90%) HP:0001762
20 breech presentation 32 HP:0001623
21 short neck 32 HP:0000470
22 telecanthus 32 HP:0000506
23 inguinal hernia 32 HP:0000023
24 intellectual disability 32 very rare (1%) HP:0001249
25 long philtrum 32 frequent (33%) HP:0000343
26 cerebellar atrophy 32 HP:0001272
27 wide nasal bridge 32 hallmark (90%) HP:0000431
28 spina bifida occulta 32 HP:0003298
29 knee flexion contracture 32 HP:0006380
30 fever 32 HP:0001945
31 joint stiffness 32 hallmark (90%) HP:0001387
32 oligohydramnios 32 occasional (7.5%) HP:0001562
33 downslanted palpebral fissures 32 hallmark (90%) HP:0000494
34 flat face 32 HP:0012368
35 high palate 32 HP:0000218
36 postnatal growth retardation 32 HP:0008897
37 blepharophimosis 32 HP:0000581
38 epicanthus 32 HP:0000286
39 feeding difficulties in infancy 32 hallmark (90%) HP:0008872
40 nasal speech 32 frequent (33%) HP:0001611
41 small for gestational age 32 HP:0001518
42 malignant hyperthermia 32 frequent (33%) HP:0002047
43 malar flattening 32 HP:0000272
44 hearing impairment 32 frequent (33%) HP:0000365
45 mask-like facies 32 HP:0000298
46 hypoplasia of the brainstem 32 HP:0002365
47 depressed nasal ridge 32 hallmark (90%) HP:0000457
48 abnormal auditory evoked potentials 32 HP:0006958
49 narrow mouth 32 hallmark (90%) HP:0000160
50 adducted thumb 32 HP:0001181

UMLS symptoms related to Arthrogryposis, Distal, Type 2a:


seizures

Drugs & Therapeutics for Arthrogryposis, Distal, Type 2a

Drugs for Arthrogryposis, Distal, Type 2a (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961
2
Menthol Approved 2216-51-5 16666
3 Analgesics
4 Anti-Arrhythmia Agents
5 Neurotransmitter Agents
6 Peripheral Nervous System Agents
7 Vasodilator Agents

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions Unknown status NCT01306994
2 Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome Recruiting NCT01144741
3 Study of Quality of Life in Freeman-Sheldon Syndrome and Related Conditions Terminated NCT01307475

Search NIH Clinical Center for Arthrogryposis, Distal, Type 2a

Genetic Tests for Arthrogryposis, Distal, Type 2a

Genetic tests related to Arthrogryposis, Distal, Type 2a:

id Genetic test Affiliating Genes
1 Freeman-Sheldon Syndrome 29 24 MYH3
2 Arthrogryposis, Distal, Type 2a 24 MYH3

Anatomical Context for Arthrogryposis, Distal, Type 2a

MalaCards organs/tissues related to Arthrogryposis, Distal, Type 2a:

39
Skin, Eye, Skeletal Muscle

Publications for Arthrogryposis, Distal, Type 2a

Variations for Arthrogryposis, Distal, Type 2a

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis, Distal, Type 2a:

71
id Symbol AA change Variation ID SNP ID
1 MYH3 p.Thr178Ile VAR_030370 rs121913619
2 MYH3 p.Glu498Gly VAR_030374
3 MYH3 p.Tyr583Ser VAR_030376
4 MYH3 p.Arg672Cys VAR_030377 rs121913618
5 MYH3 p.Arg672His VAR_030378 rs121913617
6 MYH3 p.Val825Asp VAR_030380 rs121913620

ClinVar genetic disease variations for Arthrogryposis, Distal, Type 2a:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 MYH3 NM_002470.3(MYH3): c.2015G> A (p.Arg672His) single nucleotide variant Pathogenic rs121913617 GRCh37 Chromosome 17, 10544634: 10544634
2 MYH3 NM_002470.3(MYH3): c.2014C> T (p.Arg672Cys) single nucleotide variant Pathogenic rs121913618 GRCh37 Chromosome 17, 10544635: 10544635
3 MYH3 NM_002470.3(MYH3): c.533C> T (p.Thr178Ile) single nucleotide variant Pathogenic rs121913619 GRCh37 Chromosome 17, 10553691: 10553691
4 MYH3 NM_002470.3(MYH3): c.2474T> A (p.Val825Asp) single nucleotide variant Pathogenic rs121913620 GRCh37 Chromosome 17, 10543521: 10543521
5 MYH3 NM_002470.3(MYH3): c.1504T> G (p.Tyr502Asp) single nucleotide variant Likely pathogenic rs797045727 GRCh38 Chromosome 17, 10642903: 10642903
6 MYH3 NM_002470.3(MYH3): c.850T> G (p.Tyr284Asp) single nucleotide variant Likely pathogenic rs886042111 GRCh37 Chromosome 17, 10550547: 10550547

Expression for Arthrogryposis, Distal, Type 2a

Search GEO for disease gene expression data for Arthrogryposis, Distal, Type 2a.

Pathways for Arthrogryposis, Distal, Type 2a

GO Terms for Arthrogryposis, Distal, Type 2a

Sources for Arthrogryposis, Distal, Type 2a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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