Taking a look at the rare ATR-16 Syndrome

Introduction

Often, the origin of most psychological conditions and disorders have been looked at from two distinct perspectives, based on the nature versus nurture debate. Most researchers today agree on a model for the two to be located on the two opposite ends of a continuum.

Some disorders clearly lie on either ends of this spectrum, and one such example is that of a rare congenital disorder that stems purely from the human genome, known as the ATR-16 syndrome or Alpha-Thalassemia-Intellectual disability syndrome. It is known to be caused due to gene deletion(s) in the 16th chromosome (monosomy) affecting child development, blood, as well as the brain. This deletion could be a result of a new mutation (de novo deletion) or an unbalanced chromosomal translocation.

What are chromosomes? What’s so special about chromosome 16?

Chromosomes are strand-like structures, a long DNA molecule containing the genetic material of an organism. They are also a key part of cell division, as they replicate and distribute DNA, and changes in numbers or structures of chromosomes have been linked to serious problems. They are found in pairs and humans have a total of 23 pairs of chromosomes.

Chromosome 16 is one out of these 23 pairs of chromosomes and it has been linked to providing instructions for making proteins and any missing genes or deletions have been associated with an increased risk of birth defects, developmental delay and learning disabilities.

Symptoms

The syndrome is currently still being researched and identification of symptoms specific to the disorder have proven tricky due to the comorbidity of having other related genetic defects along with deletion in Chromosome 16.

Some common symptoms that lead to diagnosis include intellectual impairments as well as physical dysmorphia in infants, though it is important to note that they may vary in combinations and extent of symptoms based on the specific case in question.

• Mild to profound Intellectual disability
• Developmental delays
• Speech delays 
• Infants with ATR-16 have a form of anemia known as alpha thalassemia, which is linked to microcytic (abnormally small) red blood cells which result in a lack of adequate functional haemoglobin
• Hypotonia which implies a diminished muscle tone
• Genitourinary abnormalities in males seen through cryptorchidism, the failure of the testes to descend

Dysmorphic features in the neonate could include:

• A small head, a condition also known as microcephaly
• Widely spaced out eyes, a condition also known as hypertelorism
• Clubfoot, a condition where an infant’s feet are rotated inward and downward
• Small ears
• Underdevelopment of the middle area of the face, also causing nasal shape distortions

Based on these symptoms, a medical professional could choose to conduct certain chromosomal tests or linkage analysis, to diagnose the individual. Sometimes, other methods such as use of comparative genomic hybridization (CGH) may also be required to identify this deletion.

Causes

While the genetic disorder is usually spontaneous, some research also suggests that it can be passed down from a parent. Spontaneous cases are referred to as ‘de novo’ and are assumed to have occurred by chance after referring to family records and genomic sequences. In such cases, it is not likely to occur again.

In case there is a chromosomal translocation found in the 16th chromosome of either parent, there is also a high chance that this could occur again with another child they have. Thus, genetic counselling during parenthood can be a good practice to combat the risk factors of these genetic disorders before pregnancy.

Treatment Methods

Since one of the main symptoms of the disorder includes intellectual disabilities and dysmorphic features, it can be identified quite early on in infancy, but must NOT be self-diagnosed or self-medicated. It is important to take the opinion of medical professionals and conduct the appropriate chromosomal testing to identify and verify the gene deletion.

Treatment is seen to be multi-dimensional and mainly targeted towards the various symptoms which may be unique to the individual. It could require different specialists from hematologists, neurologists, paediatricians, along with psychotherapists to work together and tailor a unique treatment to work on different aspects for improvement. Psychotherapists may work in specific towards aiding treatment for improving the intellectual difficulties and speech delays through the aid of speech therapy and other methods, while hematologists will focus on restoring haemoglobin levels which may require blood transfusions depending on the case. Genetic counselling may also be provided to the individual as well as the family.

Prevalence

The disorder is known to be extremely rare, with only about 20 reported cases in medical literature, though some suggest that it might be underdiagnosed. The range of symptoms make it easy for the disorder to go undiagnosed or misdiagnosed. The incidence rates do not show any significant differences among males or females.

Conclusion

A growing awareness of various practices such as genetic counselling and chromosomal testing must be raised, for disorders such as ATR-16 syndrome to be diagnosed quickly, so that adequate support and care can be provided to the patient to lead a life of better quality. Investigating other risk factors and extensive research can also help couples take adequate precautions prenatally.

Resources:

• https://rarediseases.org/rare-diseases/atr-16-syndrome/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288322/
• https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=13808&Disease_Disease_Search_diseaseType=ORPHA&Disease_Disease_Search_diseaseGroup=98791&Disease(s)/group%20of%20diseases=ATR-16-syndrome&title=ATR-16-syndrome&search=Disease_Search_Simple