Only 1 in 200 000 : Fraser syndrome, one of the rarest genetic disorders

What are genetic disorders and how does Fraser syndrome fit into that?

Genetic disorders are diseases caused by whole or partial changes in the DNA. These changes are called mutations. Genetic mutations can appear in one gene or multiple genes. They can appear during cell division where errors occur during DNA replication or they can be caused by harmful environmental mutagens (an agent that causes genetic mutations) such as radiation or harmful chemical substances.

There are believed to be over 7000 genetic disorders. Some diseases are inherited from the parents while others can develop during a persons lifetime randomly or through environmental exposure. Some examples of the most common genetic disorders are Down syndrome, Turner syndrome, sickle cell disease, cystic fibrosis etc. 

One of the rarest genetic diseases is Fraser syndrome which only affects about 1 in 200.000 newborns. Males and females are affected equally by Fraser syndrome and it is classified as a neonatal disorder which means that it develops before birth.  

What is Fraser syndrome and what causes it?

Fraser syndrome is a genetic disorder that is characterized by several malformations which appear at birth. These may include :

• Cryptothalmos - This means that the eyes are completely or partially covered in skin which can cause blindness. This happens due to the eyelids not developing properly.
• Cutaneous syndactyly - This means that the skin between the fingers or toes is fused. 
• Renal abnormalities - Abnormalities in the kidneys such as absence of one or both kidneys, improper development (dysplasia) and underdevelopment (hypoplasia).
• In affected males, Fraser syndrome can cause: cryptochidism (one or both testes fail do drop down to the scrotum), hypospadias (abnormal placement of the urinary opening) and other symptoms
• In affected females, Fraser syndrome can cause: malformed fallopian tubes, abnormally shaped uterus, closed or absent vagina and other symptoms.
• Respiratory tract abnormalities - This includes malformations of the nose or respiratory tract which can cause difficulties breathing and laryngeal stenosis or atresia (a larynx, voice box, which is narrower than usual or blocked).

These are some of the most common characteristics of Fraser syndrome. However, there are other symptoms such as anophthalmia (missing eyes), microphthalmia (small eyes), abnormal tear ducts, middle ear issues, anal issues, bifid tongue or a tongue with an indentation, dental crowding or changes in how teeth are aligned and other rare characteristics. 

Fraser syndrome can be caused by mutations in the FRAS1, FREM2 or GRIP1 genes. The FRAS1 and FREM2 genes produce proteins which work together to connect the different layers of skin together. This is a complex function which affects the development of not only the skin but also the tissue of internal organs. If there is a mutation in these genes than the proteins they create are faulty leading to improper development. The GRIP1 gene creates the GRIP1 protein. This protein helps the proteins created by the FRAS1 and FREM2 genes reach their correct location. Mutations in the GRIP1 gene prevent the normal function of the proteins created by FRAS1 and FREM2. 

The most common cause of Fraser syndrome is due to mutations in the FRAS1 gene, accounting for about half of the cases of Fraser syndrome. FREM2 and GRIP1 mutations are found less often in cases of Fraser syndrome.

Fraser syndrome is inherited by recessive genes. This means that the parent can have one of the genes but not have any of the symptoms of Fraser syndrome. If both parents carry these mutated genes then there is a high chance that their newborn will get both genes therefore having the syndrome. The chance for a child to receive both genes is about 25%.

Living with and treating Fraser syndrome

There is no cure for Fraser syndrome. It can be treated by surgery to help correct some of the issues or with the help of specialists who will evaluate what kind of help is needed. Fraser syndrome has a mixed life expectancy. Some of those with it may only survive their first year of life while others can live way into adulthood. 

TikToker Kirst or @kirstonthebrightside said:

 "I was born with an extremely rare genetic condition called Fraser Syndrome. This condition can cause several medical complications. For me, it means I am deaf blind, I have narrowing of my trachea, and I was born with complete syndactyly (webbing) of my hands and feet. It also means that I live with a visible difference.

The zebra is often used as a symbol for rare medical conditions. Life isn’t always black and white, it doesn’t always conform to straight lines, my life is certainly no exception. My life has been full of labels: ‘deaf-blind’, ‘disabled’, all of which have impacted on my sense of inclusion, and expectations of me by others. I spent many years feeling alone, never wanting to accept my condition as part of who I am, because I felt misunderstood, like I was the only one. However, sometimes having a label can give answers, shedding light on the depth of issues that can be invisible to others. So here I am, just another zebra, standing on the other side of countless surgeries/medications, with more likely to come. Your scars and stripes are testimony to your strength and uniqueness, so never be afraid to wear them with pride!"

Kirst uploads many fashion related videos showcasing her incredible and colorful style, but also sheds light on Fraser syndrome. 

Here are her socials :

Kirst | on the bright side
Kirst 🍭✨

Sources:

1. https://medlineplus.gov/genetics/condition/fraser-syndrome/#causes
2. https://www.webmd.com/children/what-is-fraser-syndrome
3. https://rarediseases.org/rare-diseases/fraser-syndrome/
4. https://www.genome.gov/For-Patients-and-Families/Genetic-Disorders
5. https://www.ncbi.nlm.nih.gov/books/NBK21114/#:~:text=Mutations%20result%20either%20from%20errors,that%20occur%20(Section%2014.2).
6. https://entrepreneurs.utoronto.ca/spotlight/this-is-the-place-to-target-genetic-diseases/