Genes

What Is Genetic Testing? Read this ->  HERE

Diagnosis:

An unbalanced chromosomal translocation between 3p25.3 and 9p21.3. This derivative chromosome shows a deletion of 3p26.3—3p25.3 (approximately 9.1 MB…which is a large deletion) and a duplication of 9p24.3-9p21.3 (23.2 MB in size). Yup. It’s a mouthful.

Since there is a reasonable amount of recent information about 3p- the focus of Avery’s disorder and treatments revolve around what we know about 3p- Syndrome. The severity of the condition and the signs and symptoms depend on the exact size and location of the deletion and which specific genes are involved.

Common symptoms shared by people (but not all) with 3p deletions may include:

poor growth, feeding difficulties, seizures, developmental delays, intellectual disabilities, autism spectrum disorder, distinctive facial features, ptosis, small head (microcephaly), and poor muscle tone (hypotonia). Most known cases, including Avery’s, are not inherited—there was a random genetic glitch somewhere along the line. People with this disorder can pass the deletion on to their children. source

Read about:  3p25- HERE and 3p26- HERE

When Avery was first diagnosed with 9p Duplication Syndrome in 2008 there wasn’t much known about this area. Today there is a lot more information. It’s interesting to note that of these common 9p+ features, Avery has every single one. 

◼ A recognisable “look” to the head and face/wide nasal bridge
◼ Some degree of developmental delay
◼ Some degree of learning disabilities, ranging from mild to profound
◼ Speech and language delay
◼ Growth delay, delayed puberty
◼ Abnormalities of the hands and feet, often mild
◼ Dental issues including: late teething, over-crowding, tooth-grinding, weak enamel
◼ Low muscle tone (hypotonia)
◼ Constipation
◼ Feeding difficulties, including reflux, which usually resolve after babyhood or early childhood
◼ Glue ear/frequent ear and respiratory infections, which usually resolve
during childhood
◼ A high, narrow palate
◼ Seizures
◼ A heart condition (in this case a mitral valve prolapse)
◼ Anomalies of the brain (an early MRI revealed a benign cyst)

FAQ:

Q: What is an unbalanced translocation?

A: When the 23 pairs of chromosomes were lining up to divide they misaligned slightly causing a small section on the end of one of the two chromosome #3s to break off. Where it went, nobody knows. At the same time, a larger section of one of the two #9 chromosomes made a duplicate copy of itself, which then attached to the end of the damaged #3. Crazy right? In short, there are genes missing from chromosome 3 and genes duplicated from chromosome 9. In theory, this should have devastating results. In reality, Avery has far surpassed everybody’s expectations. Our geneticist thinks the duplicated genes may be compensating somehow for the missing genetic material. 

Q: What is this syndrome called?

A: A syndrome is named when a number of people present with the same missing or duplicated chromosomal material. Since Avery is the only known person so far with this particular genetic combination, no “official” name is given. We’re going with Super Girl Syndrome. 🙂

Q: Why did this happen?

A: This is a completely random (de novo) occurrence. Avery’s dad and I were tested and we are not carriers. This defect in either the sperm or egg, occurred spontaneously, long before conception for reasons unknown.

Q: What affects have been observed so far?

A: Avery has global developmental delays—gross and fine motor delays, expressive and receptive language disorder/profound speech delay, significant learning delays, hypotonia, clinodactyly, attention and memory issues, extremely high tolerance for pain, and Epilepsy.

Q: What does the future hold in terms of health and learning/mental delays?

A: There are 62 genes duplicated on chromosome 9. Two of these genes are linked to forms of blood cancers. This is something to monitor by blood test every few years. 

Learning/mental Delays: Of sixteen deleted genes, three have been linked as the cause of mental delays, specifically related to memory. In early childhood, children learn many things by remembering and repeating. Avery may have trouble remembering and recalling things, therefore it takes her a longer to “learn” since she has to understand a concept fully before she can repeat it and extend upon it. Avery will need to learn in a different way or find ways around this disability.

Ataxia 15: One missing genes is responsible for this dominant disorder. There are actually 18 types of this disease. This is a disease where slowly over time, people have trouble walking and balancing. SCA15 is one of the milder and slower progressing forms. It only affects the cerebellum, not the spinal cord (some of the other forms affect both). This means that though this disorder is probable (but not definite!), it will not be as severe.

Muscular Dystrophy: Avery is missing one of the dominant genes (CAV3) linked a form of MD called Limb Girdle Muscular Dystrophy. There are several other genes involved that she DOES have intact, so there is a good chance that another gene could compensate for the missing protein and this might never become an issue. **According to her neurologist, if she hasn’t developed this disease at this point, she most likely never will. Yasssssss!

Cardiac Issues: Mutations identified in the CAV3 gene can also lead to Hyperkalemia or rippling muscle disease. Other mutations in Caveolin causes Long QT Syndrome-9. Avery is tested for this disorder on a yearly basis and precautions are taken in terms of medications prescribed in order to limit the chance of promoting an arrhythmia. She also has a heart murmur and mitral valve prolapse.