MCID: ART061
MIFTS: 45

Arthrogryposis, Distal, Type 2a

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

Aliases & Classifications for Arthrogryposis, Distal, Type 2a

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

Name: Arthrogryposis, Distal, Type 2a 53 13
Freeman-Sheldon Syndrome 53 24 55 71 28 69
Craniocarpotarsal Dystrophy 53 49 24 55 71
Craniocarpotarsal Dysplasia 53 49 24 55 71
Whistling Face-Windmill Vane Hand Syndrome 53 49 24 71
Da2a 53 49 24 71
Fss 53 49 24 71
Distal Arthrogryposis Type 2a 49 55
Whistling Face Syndrome 24 55
Distal Arthrogryposis, Type 2a 24
Freeman-Sheldon Syndrome; Fss 53
Arthrogryposis Distal Type 2a 49
Arthrogryposis, Distal, 2a 71
Freeman Sheldon Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
freeman-sheldon syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

53
Miscellaneous:
breech presentation
see also da2b , which is an allelic disorder
autosomal recessive form has also been described

Inheritance:
autosomal dominant


HPO:

31
arthrogryposis, distal, type 2a:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 2a

NIH Rare Diseases : 49 Freeman Sheldon syndrome is a disorder present from birth (congenital) characterized by joint deformities (contractures) that restrict movement in the hands and feet and abnormalities of the head and face. People with this syndrome have a small mouth (microstomia) with pursed lips, giving the appearance of a "whistling face." Other facial features may include a prominent forehead and brow ridges, a short nose and area between the nose and mouth, widely spaced eyes (hypertelorism), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and a small tongue (microglossia) and jaw (micrognathia).  People with Freeman Sheldon syndrome often have speech, eating, and respiratory problems and may also experience hearing loss, and growth and development delay. Other symptoms include club foot, joint contracture, hand and feet defects, and scoliosis. There is an increased risk for individuals with this disorder to develop a severe reaction to certain drugs used during surgery (malignant hyperthermia). Freeman Sheldon syndrome can be caused by mutations in the MYH3 gene; however, not all individuals have a mutation within this gene. Some cases are inherited in an autosomal dominant manner, while others are inherited in an autosomal recessive manner, and still others occur randomly with no apparent cause (sporadically). Although there is no specific treatment or cure, it is possible to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person. Last updated: 2/13/2018

MalaCards based summary : Arthrogryposis, Distal, Type 2a, also known as freeman-sheldon syndrome, is related to arthrogryposis, distal, type 5 and distal arthrogryposis, and has symptoms including joint stiffness, hypertelorism and ptosis. 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 eye, tongue and skin.

OMIM : 53 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)

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.

Genetics Home Reference : 24 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."

Related Diseases for Arthrogryposis, Distal, Type 2a

Graphical network of the top 20 diseases related to Arthrogryposis, Distal, Type 2a:



Diseases related to Arthrogryposis, Distal, Type 2a

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 2a

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
mental retardation (31%)

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

Skeletal Pelvis:
hip dislocation
hip contractures

Skeletal Spine:
spina bifida occulta
kyphoscoliosis

Metabolic Features:
malignant hyperthermia
hyperpyrexia, usually associated with anesthesia

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

Growth Weight:
low birth weight

Muscle Soft Tissue:
mild muscle weakness
skeletal muscle biopsy shows fiber size variability
type 1 fiber type predominance
small type 1 fibers
increased interstitial connective tissue

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

Head And Neck Neck:
short neck

Genitourinary External Genitalia Male:
inguinal hernia

Head And Neck Face:
long philtrum
flat face
mask-like facies
full forehead
h-shaped chin dimple
more
Voice:
nasal speech

Head And Neck Mouth:
pursed lips
small mouth

Skeletal Hands:
camptodactyly
ulnar deviation
cortical thumbs

Skeletal Feet:
vertical talus
equinovarus
contracted toes

Skeletal Limbs:
knee contractures
shoulder contractures

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


Clinical features from OMIM:

193700

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

55 31 (show top 50) (show all 71)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 55 31 hallmark (90%) Very frequent (99-80%) HP:0001387
2 hypertelorism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000316
3 ptosis 55 31 frequent (33%) Frequent (79-30%) HP:0000508
4 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
5 neurological speech impairment 55 31 frequent (33%) Frequent (79-30%) HP:0002167
6 scoliosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0002650
7 hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000365
8 abnormality of the dentition 55 31 hallmark (90%) Very frequent (99-80%) HP:0000164
9 wide nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0000431
10 short stature 55 31 frequent (33%) Frequent (79-30%) HP:0004322
11 feeding difficulties in infancy 55 31 hallmark (90%) Very frequent (99-80%) HP:0008872
12 long philtrum 55 31 frequent (33%) Frequent (79-30%) HP:0000343
13 hernia 55 31 occasional (7.5%) Occasional (29-5%) HP:0100790
14 strabismus 55 31 frequent (33%) Frequent (79-30%) HP:0000486
15 cryptorchidism 55 31 frequent (33%) Frequent (79-30%) HP:0000028
16 underdeveloped nasal alae 55 31 hallmark (90%) Very frequent (99-80%) HP:0000430
17 depressed nasal ridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0000457
18 deeply set eye 55 31 frequent (33%) Frequent (79-30%) HP:0000490
19 downslanted palpebral fissures 55 31 hallmark (90%) Very frequent (99-80%) HP:0000494
20 narrow mouth 55 31 hallmark (90%) Very frequent (99-80%) HP:0000160
21 polyhydramnios 55 31 occasional (7.5%) Occasional (29-5%) HP:0001561
22 nasal speech 55 31 frequent (33%) Frequent (79-30%) HP:0001611
23 talipes equinovarus 55 31 hallmark (90%) Very frequent (99-80%) HP:0001762
24 oligohydramnios 55 31 occasional (7.5%) Occasional (29-5%) HP:0001562
25 camptodactyly of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0100490
26 ulnar deviation of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0009465
27 prenatal movement abnormality 55 31 frequent (33%) Frequent (79-30%) HP:0001557
28 malignant hyperthermia 55 31 frequent (33%) Frequent (79-30%) HP:0002047
29 absent palmar crease 55 31 occasional (7.5%) Occasional (29-5%) HP:0010489
30 fever 31 HP:0001945
31 seizures 31 HP:0001250
32 muscle weakness 31 HP:0001324
33 malar flattening 31 HP:0000272
34 short neck 31 HP:0000470
35 high palate 31 HP:0000218
36 intellectual disability 31 very rare (1%) HP:0001249
37 inguinal hernia 31 HP:0000023
38 mandibular prognathia 31 HP:0000303
39 short nose 31 HP:0003196
40 microcephaly 31 HP:0000252
41 prominent forehead 31 HP:0011220
42 epicanthus 31 HP:0000286
43 flat face 31 HP:0012368
44 growth delay 55 Very frequent (99-80%)
45 postnatal growth retardation 31 HP:0008897
46 mask-like facies 31 HP:0000298
47 arthrogryposis multiplex congenita 31 HP:0002804
48 telecanthus 31 HP:0000506
49 hip dislocation 31 HP:0002827
50 blepharophimosis 31 HP:0000581

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)
# 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:


# 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:

# Genetic test Affiliating Genes
1 Freeman-Sheldon Syndrome 28 MYH3

Anatomical Context for Arthrogryposis, Distal, Type 2a

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

38
Eye, Tongue, Skin, Skeletal Muscle

Publications for Arthrogryposis, Distal, Type 2a

Articles related to Arthrogryposis, Distal, Type 2a:

(show top 50) (show all 77)
# Title Authors Year
1
Molecularly proven mosaicism in phenotypically normal parent of a girl with Freeman-Sheldon Syndrome caused by a pathogenic MYH3 mutation. ( 26996280 )
2016
2
Surgical Approach, Findings, and Eight-Year Follow-Up in a Twenty-Nine Year Old Female With Freeman-Sheldon Syndrome Presenting With Blepharophimosis Causing Near-Complete Visual Obstruction. ( 27380584 )
2016
3
The Most Prevalent Freeman-Sheldon Syndrome Mutations in the Embryonic Myosin Motor Share Functional Defects. ( 26945064 )
2016
4
The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle. ( 25740846 )
2015
5
Freeman-Sheldon Syndrome Presenting with Microstomia: A Case Report and Literature Review. ( 24431877 )
2013
6
Anaesthesia challenges in Freeman-Sheldon syndrome. ( 24403637 )
2013
7
A novel TNNI2 mutation causes Freeman-Sheldon syndrome in a Chinese family with an affected adult with only facial contractures. ( 23850728 )
2013
8
Freeman-sheldon syndrome. ( 23277889 )
2013
9
A further heterogeneous locus contained in 8q21 for Freeman-Sheldon syndrome may be suggested by Kristin Hofmann. ( 23486078 )
2013
10
Freeman Sheldon syndrome with marked kyphoscoliosis at birth: a case report. ( 23416834 )
2013
11
Improving oral function and cosmesis in a case of Freeman-Sheldon syndrome. ( 24225909 )
2013
12
Freeman-Sheldon syndrome: combined surgical and non-surgical approach. ( 23218872 )
2013
13
Freeman-Sheldon syndrome: a dental perspective. ( 24021330 )
2013
14
Anesthetic management of a patient with Freeman-Sheldon syndrome: case report and literature review. ( 22340578 )
2012
15
Severe skew foot deformity in a patient with freeman-sheldon syndrome. ( 22383916 )
2011
16
p.R672C mutation of MYH3 gene in an Egyptian infant presented with Freeman-Sheldon syndrome. ( 20924721 )
2011
17
Freeman-Sheldon syndrome: case report and review of the literature. ( 21986849 )
2011
18
Surgical and prosthodontic rehabilitation in a patient with Freeman-Sheldon syndrome. ( 20856050 )
2010
19
Freeman-Sheldon syndrome with cerebral venous thrombosis: is it a coincidence? ( 20393251 )
2010
20
Freeman-Sheldon syndrome--prenatal and postnatal diagnosis. ( 20012803 )
2010
21
Frontal bandeau reconstruction with a fibula flap in a patient with Freeman-Sheldon syndrome. ( 19165042 )
2009
22
Freeman-Sheldon syndrome: a functional and cosmetic correction of microstomia. ( 19008166 )
2009
23
Anaesthetic management of a child with Freeman-sheldon syndrome undergoing spinal surgery. ( 18361019 )
2008
24
Freeman-Sheldon syndrome. A case report and review of the literature. ( 18677448 )
2008
25
Anesthetic management of a patient with Freeman-Sheldon syndrome: case report. ( 17967677 )
2007
26
Mutations in embryonic myosin heavy chain (MYH3) cause Freeman- Sheldon syndrome and Sheldon-Hall syndrome. ( 16642020 )
2006
27
Clinical characteristics and natural history of Freeman-Sheldon syndrome. ( 16510655 )
2006
28
Prenatal diagnosis of Freeman-Sheldon syndrome and usefulness of an ultrasound fetal lip width normogram. ( 16715537 )
2006
29
Combined spinal-epidural anesthesia for a child with Freeman-Sheldon syndrome with difficult airway. ( 17122295 )
2006
30
Neuroleptic malignant syndrome induced by metoclopramide in an infant with Freeman-Sheldon syndrome. ( 16931708 )
2006
31
Freeman-Sheldon syndrome: a case report. ( 17014544 )
2006
32
Freeman-Sheldon syndrome: dental and orthodontic implications. ( 15926447 )
2005
33
Freeman-Sheldon syndrome. ( 16085975 )
2005
34
Anesthesia for Freeman-Sheldon syndrome using a folded laryngeal mask airway. ( 16037204 )
2005
35
Freeman-Sheldon syndrome. ( 15829002 )
2005
36
Awake nasotracheal intubation using fiberoptic bronchoscope in a pediatric patient with Freeman-Sheldon syndrome. ( 16101713 )
2005
37
Freeman-Sheldon syndrome: report of one case. ( 16640009 )
2005
38
Anesthetic management of a patient with Freeman-Sheldon syndrome. ( 15385019 )
2004
39
Laryngomalacia, choanal atresia and renal anomaly in a newborn with Freeman-Sheldon syndrome phenotype. ( 15517834 )
2004
40
Surgical management of the hand in Freeman-Sheldon syndrome. ( 12792532 )
2003
41
Freeman-Sheldon syndrome: a case report. ( 12731619 )
2003
42
Functional upper airway obstruction in a child with Freeman-Sheldon syndrome. ( 11891401 )
2002
43
Sleep disordered breathing during REM sleep in Freeman-Sheldon syndrome. ( 11125756 )
2000
44
Anesthesia for Freeman-Sheldon syndrome using a laryngeal mask airway. ( 10451140 )
1999
45
Anaesthetic management of a patient with Freeman Sheldon syndrome. ( 9549749 )
1998
46
Generalised muscle hypertonia with mask-like face (Freeman-Sheldon syndrome) in a Tanzanian girl. ( 9788734 )
1998
47
Clinical analysis of a variant of Freeman-Sheldon syndrome (DA2B). ( 9508073 )
1998
48
Freeman-Sheldon syndrome: case management from age 6 to 16 years. ( 9138511 )
1997
49
A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter. ( 9012416 )
1997
50
Freeman Sheldon syndrome: severe upper airway obstruction requiring neonatal tracheostomy. ( 9220529 )
1997

Variations for Arthrogryposis, Distal, Type 2a

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

71
# 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
# 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
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
Content
Loading form....