Costello syndrome
Costello syndrome | |
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Other names | Faciocutaneoskeletal syndrome |
Costello syndrome is inherited in an autosomal dominant manner. | |
Specialty | Medical genetics |
Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare
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
Costello syndrome is caused by any of at least five different mutations in the
HRAS is a
Costello syndrome is inherited in an
Diagnosis
Costello Syndrome can be difficult for doctors to immediately clinically diagnose, as there are similar conditions that resemble this syndrome. A physician will start by assessing the child's height, the size of the head, and birth weight.[citation needed]
Full genome and Exome next generation DNA testing is the primary diagnostic tool for Costello Syndrome.[citation needed]
Treatments
At the 2005
Another medication that affects H-Ras is Lovastatin, which is planned as a treatment for neurofibromatosis type I. When this was reported in mainstream news, the Costello Syndrome Professional Advisory Board was asked about its use in Costello Syndrome. Research into the effects of Lovastatin was linked with Alcino Silva, who presented his findings at the 2007 symposium. Silva also believed that the medication he was studying could help children with Costello syndrome with cognition.[citation needed]
A third medication that might help children with Costello syndrome is a MEK inhibitor that helps inhibit the pathway closer to the cell nucleus.[citation needed]
Research
Spanish researchers reported the development of a Costello mouse, with the G12V mutation, in early 2008.[5] 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.[6] 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.[7] These mutations, along with mutations that cause cardiofaciocutaneous syndrome, found soon after, surprised geneticists and changed how genetic syndromes can be grouped.[citation needed] Before this, geneticists looked for new mutations in genes with mutations that caused syndromes similar to the unknown syndrome.[citation needed] For example, researchers looked at 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 identified as one of the Costello syndrome 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
References
- ISBN 0-7216-2921-0.
- ^ "Cs description". Archived from the original on 2010-11-21. Retrieved 2010-12-29.
- ^ "Discovery offers key to children's disease". The New Zealand Herald. 24 October 2003. Retrieved 26 September 2011.
- S2CID 24745057.
- PMID 18483625.
- PMID 19132118.
- S2CID 22119631.
- ^ Lisa Schoyer, 2007 Costello syndrome medical symposium.
Some text in this article was originally taken from http://ghr.nlm.nih.gov/condition=costellosyndrome, a public domain source