John Langdon Down, an English physician, identified Down syndrome in 1866. It was not until nearly 100 years later, in Paris, that Dr. Jerome Lejeune established the link between Down syndrome and chromosome 21.

What is down syndrome?

The most common type of chromosomal abnormality in humans is due to the presence of a third copy of chromosome 21, as a part or whole. Furthermore, this additional copy follows the term of “Down syndrome”, and it’s the most occurring live born aneuploidy ever. To clarify, aneuploidy means the existence of extra, or the absence of a chromosome. Normally, the embryo is created from the genetic material coming from the mother and the father. Thus, a 23 pairs of chromosomes making 46 chromosomes in total is the normal case, in which half is received from each parent. When one of the chromosomes fails to separate, a partial extra copy or a whole extra copy of a chromosome will result in 3 copies instead of the normal 2. Hence, Down syndrome occurs as a result of this disassembly.

Down syndrome types:

Nondisjunction (Trisomy 21): A condition known as non-disjunction results in an embryo containing three copies of chromosome 21, rather than the usual two. To illustrate, this occurs when a pair of 21st chromosomes can't separate in either the sperm or the egg before or during conception.

Translocation: Robertsonian translocation and isochromosome or “ring chromosome”: Translocations account for about 4% of cases of Down syndrome where the cells maintain 46 chromosomes in total. However, chromosome 21 is usually added to chromosome 14. Consequently, it's because of the presence of an extra piece (part or full) of chromosome 21 that Down syndrome occurs.

Mosaicism: Research indicates individuals with mosaic Down syndrome might have fewer symptoms compared to individuals with other types of Down syndrome. As a matter of fact, mosaicism makes up about 1% of all cases of Down syndrome.

Causes of down syndrome:

• A third copy of chromosome 21.
• Imbalance in gene dosage: an increase in gene expansion because of Hsa21 gene number or dose rise.
• Possible associations between different genes and different down syndrome phenotypes
  A number of trisomy genes create a genetic imbalance and result in higher impact on expression and regulation of many genes.
• There are a few Down syndrome critical regions on 21q21.22, which are associated with partial trisomy for Has21.

Symptoms of down syndrome:

Physical features:

• A face that looks flat, most noticeable in the nose area
• Eyelids are slant upwards
• Brush field's spots (white spots on the iris of the eye)
• Significant skin folds that go between the eyes and the nose
• Neck is short and ears are small
• Tongue sticks out
• Palmar crease (a single line in the hand palm)
• Hands and feet are small
• Shorter than others of the same age
• Tiny pinky finger that might twist towards the thumb
• Loose joints or weak muscle tone

Medical:

• Clouded eyes “Cataracts”
• Prone to infections including skin infections, respiratory and urinary system infection
• Congenital cardiac defects
• Vision abnormality
• Loss of hearing
• Dislocations of hip
• Chronic constipation
• Leukemia
• Trouble breathing during sleep “Sleep apnea”
• Thyroid malfunction
• Short memory and inconsistent thinking “Dementia”
• Overweight and obesity
• Chewing issues due to late teeth growth
• Late age Alzheimer’s disease

Social and mental:

Without doubt, Down syndrome people usually develop slowly, and have a developmental delay to some level. Indeed, delays that associate with social and mental state of the patient are shaped as:

• Slow learning
• Short focus or attention duration
• Hasty personality
• Wrong judgement

What it’s like living with a down syndrome:

Down syndrome is the most prevalent genetic disease, and a Down syndrome baby is born every 700 childbirths. Thanks to the medical improvement at many aspects, patients can be adults and live up to 60 years. Without doubt, there are various degrees of intellectual disability among children with Down syndrome, and these children often have greater health complications than their peers.

Meanwhile, the progress over the past few decades, and the enhancement to come next, has all made sure to improve expectancy, satisfaction, and quality of life for these children. With advances in medical care and early intervention programs, children with Down syndrome and their families can have a healthy and productive life. In other words, this happens when they receive regular health supervision by family physicians. In fact, studies show that early intervention programs including speech, visual, physical, and occupational therapy as well as child psychology, can all promote healthy development.

Down syndrome diagnosis during pregnancy:

To begin with, there are numerous methods for diagnosing Down syndrome prenatally.

-It is possible to use ultrasound between 14 and 24 weeks of gestation to diagnose Down syndrome depending on soft markers, including:

• The increase in the thickness of the nuchal fold
• The presence of small or the absence of nasal bone
• The big size of the ventricles

-Amniocentesis and chorionic villus sampling are both medical tests that detect any chromosomal abnormality of the fetus during pregnancy. Despite the widespread use of these methods for the diagnosis, there is a 0.5% to 1% risk of miscarriages.

-Diagnosis of down syndrome through FISH of interphase nuclei using specific probes for Hsa21 gene or using the whole Hsa21.

-There is also another technique known as QF-PCR, which is based upon DNA polymorphic markers to identify the presence of 3 distinct alleles. However, this method is successful if the markers are informative and DNA is available.

-An STR analysis (Short Tandem Repeat) compares DNA sequences at selected loci in samples in order to identify genetic differences in the samples. Besides, the STR analysis has been found to identify up to 86.67% of cases.

-In paralogue sequence quantification (PSQ), the target chromosome number abnormalities are detected by using the paralogue sequence on Hsa21. Also, it is a PCR-based approach.

-At last, Non-invasive prenatal testing (NIPT) is a very trustworthy screening test to diagnose trisomy 21.

Treatment:

Above all, in order to confirm a Down syndrome diagnosis, newborns with suspicion of having Down syndrome should have a karyotyping done. Hence, it is recommended that both parents receive genetic testing and counseling from a clinical geneticist. A key aspect of Down syndrome management is to educate parents about the disorders that may accompany it in order to diagnose and treat them accordingly.
In general, treatment of Down syndrome patients is symptomatic and there is no guarantee of complete recovery.

• Hearing and vision assessments are needed to detect cataract early.
• Cataract surgery is recommended as they are more likely to develop one.
• Addressing abnormal thyroid function if detected upon yearly testing.
• In order for the child to gain weight and grow properly, he or she needs a balanced diet, regular exercise, and physical therapy.
• Even if the patient doesn’t show symptoms of congenital heart disease, cardiovascular referral should be sent.
• If there exist a congenital heart disease, the child should have a corrective procedure within the first 6 months of life to ensure optimum growth and development.

Which doctors must also follow up with a Down syndrome patient?

• Speech and language therapist
• Audiologist
• Physical and occupational therapist
• Developmental pediatrician
• Pediatric pulmonologist
• Gastroenterologist
• Neurologist
• Neurosurgeon
• Orthopedic specialist
• Child psychiatrist

References:

-CMDSS “types-syndrome”

-CDC “Down syndrome”

-Healthline “Down syndrome”

-Akhtar F, Bokhari SRA. Down Syndrome. [Updated 2021 Dec 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

-Wang, Dongbo et al. Chinese journal of medical genetics vol. 39,3 (2022): 257-263. doi:10.3760/cma.j.cn511374-20210512-00403

-Parizot E, Dard R, Janel N, Vialard F. Down syndrome and infertility: what support should we provide?. J Assist Reprod Genet. 2019;36(6):1063-1067. doi:10.1007/s10815-019-01457-2

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