Cardiospondylocarpofacial syndrome

Cardiospondylocarpofacial syndrome
Other names	Forney syndrome, Forney-Robinson-Pascoe syndrome, Mitral regurgitation-deafness-skeletal anomalies syndrome, Mitral regurgitation-hearing loss-skeletal anomalies syndrome.
Cardiospondylocarpofacial syndrome has an autosomal dominant form of inheritance.
Symptoms	Vertebral anomalies, brachydactyly, conductive hearing loss, high palate, mitral regurgitation, mitral valve prolapse, short stature, short palms, and carpal bone synostosis.[1]
Causes	Autosomal dominant mutations of the MAP3K7 gene.[1]
Diagnostic method	Genetic testing.
Frequency	Only 12 cases worldwide.[2]

Cardiospondylocarpofacial syndrome is a very rare genetic disorder which is characterized by cardiac, digital, osseous anomalies with facial dysmorphisms. Cardiospondylocarpofacial syndrome is believed to be caused by autosomal dominant mutations of the MAP3K7 gene.^[3]

Signs and symptoms

Cardiospondylocarpofacial syndrome manifests itself in many different areas of the body. It causes heart defects, multiple congenital anomalies, and dysmorphic features. The following is a list of the symptoms most commonly exhibited:^[1]

• Variable vertebral anomalies
• Brachydactyly
• Conductive hearing loss
• High palate
• Mitral regurgitation
• Mitral valve prolapse
• Short stature, nearing dwarfism
• Short palms
• Carpal bone synostosis

Less common symptoms include:

• Failure for permanent teeth to erupt
• Teeth misalignment
• Horseshoe kidney
• Dentition anomalies
• Ocular anomalies
• Nostril anteversion
• Epiphysis in the shape of a cone

• Decreased testes size (males)
• Skeletal maturation delay
• Feeding difficulties
• Freckles
• Apple cheeks
• Gastroesophageal reflux
• Hypertelorism
• Joint hypermobility
• Long philtrum
• Rotated ears
• Pseudoepiphyses
• High frequency of middle ear infections
• Rib synostosis
• Scoliosis
• Small foot
• Strabismus
• Tarsal synostosis
• Telecanthus
• Upslanted palpebral fissures
• Broad nasal bridge
• Vesicoureteral reflux

Causes

It is caused by autosomal dominant mutations of the MAP3K7 gene in the long arm of chromosome 6.^[4][3]

Epidemiology

Only 12 cases worldwide have been described in medical literature.^[2]

References

1. "Mitral regurgitation, conductive deafness, and fusion of cervical vertebrae and of carpal and tarsal bones". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. U.S. National Institutes of Health. 2021-06-16. Archived from the original on 16 June 2021. Retrieved 2022-06-12.
2. "Cardiospondylocarpofacial (CSCF) Syndrome". Online Mendelian Inheritance in Man (OMIM). 157800. Retrieved 2022-06-13.
3. Le Goff C, Rogers C, Le Goff W, Pinto G, Bonnet D, Chrabieh M, et al. (August 2016). "Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome". American Journal of Human Genetics. 99 (2): 407–413. doi:10.1016/j.ajhg.2016.06.005. PMC 4974068. PMID 27426734.
4. Morlino S, Castori M, Dordoni C, Cinquina V, Santoro G, Grammatico P, et al. (April 2018). "A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder". European Journal of Human Genetics. 26 (4): 582–586. doi:10.1038/s41431-017-0079-x. PMC 5891500. PMID 29467388.