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Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A(CPSFS1A)

MedGen UID:
401232
Concept ID:
C1867440
Disease or Syndrome
Synonyms: Contractures, pterygia, and variable skeletal fusions syndrome 1A; CPSFS1A; Distal arthrogryposis type 8; MULTIPLE PTERYGIUM SYNDROME, AUTOSOMAL DOMINANT; Multiple Pterygium Syndrome, Dominant; PTERYGIUM SYNDROME, MULTIPLE
SNOMED CT: Distal arthrogryposis type 8 (771269000); Autosomal dominant multiple pterygium syndrome (771269000)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): MYH3 (17p13.1)
 
Monarch Initiative: MONDO:0008338
OMIM®: 178110
Orphanet: ORPHA65743

Definition

Contractures, pterygia, and spondylocarpotarsal fusion syndrome-1A (CPSFS1) is characterized by contractures of proximal and distal joints, pterygia involving the neck, axillae, elbows, and/or knees, as well as variable vertebral, carpal, and tarsal fusions and short stature. Progression of vertebral fusions has been observed, and inter- and intrafamilial variability has been reported (Carapito et al., 2016; Zieba et al., 2017; Cameron-Christie et al., 2018). An autosomal recessive form of CPSFS (CPSFS1B; 618469) is caused by compound heterozygous mutation in the MYH3 gene. [from OMIM]

Clinical features

From HPO
Arthrogryposis multiplex congenita
MedGen UID:
2455
Concept ID:
C0003886
Finding
Multiple congenital contractures in different body areas.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Spondylolisthesis
MedGen UID:
52470
Concept ID:
C0038016
Disease or Syndrome
Spondylolisthesis is defined as forward slipping of a vertebral body on the one below it. Spondylolysis is defined as a defect in the pars interarticularis without vertebral slipping (summary by Wiltse et al., 1975).
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Barrel-shaped chest
MedGen UID:
120497
Concept ID:
C0264172
Finding
A rounded, bulging chest that resembles the shape of a barrel. That is, there is an increased anteroposterior diameter and usually some degree of kyphosis.
Tarsal synostosis
MedGen UID:
539393
Concept ID:
C0265654
Congenital Abnormality
Synostosis (bony fusion) involving one or more bones of the tarsus (calcaneus, talus, cuboid, navicular, cuneiiform bones).
Hemivertebrae
MedGen UID:
82720
Concept ID:
C0265677
Congenital Abnormality
Absence of one half of the vertebral body.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Hip contracture
MedGen UID:
140815
Concept ID:
C0409354
Acquired Abnormality
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A bent (flexed) knee joint that cannot be straightened actively or passively.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Carpal synostosis
MedGen UID:
98468
Concept ID:
C0431863
Congenital Abnormality
Synostosis (bony fusion) involving one or more bones of the carpus (scaphoid, lunate, triquetrum, trapezium, trapezoid, capitate, hamate, pisiform).
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Long nasal bridge
MedGen UID:
331712
Concept ID:
C1834320
Finding
Increased superior-inferior length of the nasal bridge, which is the saddle-shaped area that includes the nasal root and the lateral aspects of the nose.
Low-set, posteriorly rotated ears
MedGen UID:
387834
Concept ID:
C1857486
Finding
Ears that are low-set and posteriorly rotated.
Multiple pterygia
MedGen UID:
357990
Concept ID:
C1867448
Finding
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Vertebral fusion
MedGen UID:
480139
Concept ID:
C3278509
Anatomical Abnormality
A developmental defect leading to the union of two adjacent vertebrae.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.

Recent clinical studies

Etiology

Zhang J, Chen WQ, Wang SW, Wang SX, Yu M, Guo Q, Yu YD
Mol Genet Genomic Med 2020 Oct;8(10):e1440. Epub 2020 Aug 7 doi: 10.1002/mgg3.1440. PMID: 32767732Free PMC Article

Diagnosis

Zhang J, Chen WQ, Wang SW, Wang SX, Yu M, Guo Q, Yu YD
Mol Genet Genomic Med 2020 Oct;8(10):e1440. Epub 2020 Aug 7 doi: 10.1002/mgg3.1440. PMID: 32767732Free PMC Article

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