Medicine:Costello syndrome

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Costello syndrome
Other namesFaciocutaneoskeletal syndrome
The facial features of a teenager with Costello syndrome.

Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and intellectual disabilities, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet.[1]: 571  Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy. Beginning in early childhood, people with specific mutations on the Costello syndrome gene variant have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma).

Costello syndrome was discovered by Jack Costello, a New Zealand paediatrician, in 1977.[2][3] He is credited with first reporting the syndrome in the Australian Paediatric Journal, Volume 13, No.2 in 1977.[4]

Signs and symptoms

This condition is characterized by delayed development and intellectual disability, loose folds of skin (which are especially noticeable on the hands and feet), unusually flexible joints, and distinctive facial features including a large mouth with full lips. Others also include heart abnormalities. Infants born with this condition may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones.

Genetics

Diagnosis

Costello Syndrome can be difficult for doctors to immediately clinically diagnose, as there are similar conditions that resemble this syndrome. This condition is usually diagnosed in childhood, and the assessment starts by assessing the child's height, the size of the head, and birth weight. . In suspected prenatal cases, sonography is performed to look for polyhydramnios, increased nuchal thickness, ulnar deviation of the wrists, and decreased length of the femur and humeri.[5]


Treatments

Research

Spanish researchers reported the development of a Costello mouse, with the G12V mutation, in early 2008.[6] Although the G12V mutation is rare among children with Costello syndrome, and the G12V mouse does not appear to develop tumors as expected, information about the mouse model's heart may be transferable to humans.

Italian and Japanese researchers published their development of a Costello zebrafish in late 2008, also with the G12V mutation.[7] The advent of animal models may accelerate identification of treatment options.

Historical

That genetic mutations in HRAS cause Costello syndrome was first reported in 2005.[8] These mutations, along with mutations that cause cardiofaciocutaneous syndrome, found soon after, surprised geneticists and changed how genetic syndromes can be grouped. Before this, geneticists looked for new mutations in genes with mutations that caused syndromes similar to the unknown syndrome.{{Citation needed|date=October 2009} and around the most common Noonan syndrome mutation, PTPN11, but did not find anything related to Costello syndrome or cardiofaciocutaneous syndrome.[citation needed] The first mutation that is now ide me alleles was found unexpectedly when Japanese researchers used the DNA of children with Costello syndrome as a control, looking for another Noonan gene

Geneticists realized that the syndromes they were grouping together clinically according to their signs and symptoms were related in a way they had never realized: the mutations that cause Costello syndrome, Noonan syndrome and cardiofaciocutaneous syndromes are linked by their cellular function, not by being on or close to a gene with a known mutation. The cellular function that links them is a common signalling pathway that brings information from outside the cell to the nucleus. This pathway is called the Ras-MAP-kinase signal transduction pathway (Ras-MAPK Pathway).[9]

References

  1. ↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  2. ↑ "Cs description". http://costellokids.com/cs_description/about.htm. 
  3. ↑ "Discovery offers key to children's disease". The New Zealand Herald. 24 October 2003. http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=3530432. 
  4. ↑ Costello JM (June 1977). "A new syndrome: mental subnormality and nasal papillomata". Aust Paediatr J 13 (2): 114–8. doi:10.1111/j.1440-1754.1977.tb01135.x. PMID 907573. 
  5. ↑ Ngulube, Maria; Sharma, Sanjeev (11 February 2025). "Faciocutaneoskeletal Syndrome (Costello Syndrome)" (in en). https://www.statpearls.com/point-of-care/163569. 
  6. ↑ Schuhmacher, A.; Guerra, C.; Sauzeau, V.; Cañamero, M.; Bustelo, X.; Barbacid, M. (2008). "A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition". The Journal of Clinical Investigation 118 (6): 2169–2179. doi:10.1172/JCI34385. PMID 18483625. PMC 2381749. https://digital.csic.es/bitstream/10261/59310/1/A%20mouse%20model.pdf. 
  7. ↑ Santoriello, C.; Deflorian, G.; Pezzimenti, F.; Kawakami, K.; Lanfrancone, L.; D'adda Di Fagagna, F.; Mione, M. (2009). "Expression of H-RASV12 in a zebrafish model of Costello syndrome causes cellular senescence in adult proliferating cells". Disease Models & Mechanisms 2 (1–2): 56–67. doi:10.1242/dmm.001016. PMID 19132118. 
  8. ↑ Aoki, Y.; Niihori, T.; Kawame, H.; Kurosawa, K.; Ohashi, H.; Tanaka, Y.; Filocamo, M.; Kato, K. et al. (2005). "Germline mutations in HRAS proto-oncogene cause Costello syndrome". Nature Genetics 37 (10): 1038–1040. doi:10.1038/ng1641. PMID 16170316. 
  9. ↑ Lisa Schoyer, 2007 Costello syndrome medical symposium.

Some text in this article was originally taken from [1], a public domain source

Classification
External resources



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