7. Chromosomal pathology. Chromosomal diseases associated with numerical aberrations of autosomes, complete and mosaic forms. Medical genetic consultation (MGC).

Numerical chromosome anomalies- Down, Patau, Edwards syndromes

Numerical chromosome anomalies are associated with immediate phenotype expression and short life span. They are called aneuploidy (an abnormal number of chromosomes), and occurs when an individual either is missing a chromosome from a pair (monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.).

Down syndrome

• Also called Trisomy 21, is usually caused by the non-disjunction of the 21st chromosome during meiosis, leading to an offspring with three 21 chromosomes. It is usually a de novo mutation.
• About 95% of cases are due to an extra chromosome given by the mother
• 2/3 of these cases result in spontaneous abortions
• Incidence correlates strongly with the age of the mother; 1/46 in women over 45 years old.
• Incidence in the general population is 1/700.

There are 3 forms of Down syndrome;

1. Standard trisomy 21; due to non-disjunction of chromosomes during meiosis,
2. Translocational form; the extra 21 chromosome is attached onto another chromosome, eg. usually 14, but also 15,21 or 22. It is called a Robertsonian translocation, as it occurs between 2 acrocentric chromosomes. The affected individual still has 46 chromosomes, BUT 3 copies of chromosome 21. Parental analysis should be done to locate the translocation, as the risk of recurrence when the translocation is in the mother is 10-15%, whereas if its in the father the risk is about 2.5%. If the child has a rare 21:21 translocation he/she will definitely have Down syndrome.
3. Mosaic form; some cells are normal some have trisomy 21, due to non-disjunction during mitosis in the zygote.

Clinical features

1. Brachycephaly (shorter head)
2. Unslanted palpebral fissures
3. Ocular hypertelorism- widely spaced eyes
4. Round face and flat nasal bridge
5. Small mouth, protruding tongue
6. Mental retardation
7. Short hands and fingers
8. Thickened nuchal fold
9. Single palmar creases
10. Sandal toes
11. Congenital heart defects
12. Duodenal atresia
13. Small stature

Males with Down syndrome are infertile, whereas women are able to reproduce but have decreased fertility and 50% chance to have a child with the same disease. They usually have a good life expectancy unless they present with severe abnormalities such as heart defects.

In cases where the individual presents with Down syndrome phenotype, we draw blood and examine their karyotype. In cases in which the parents have already had a child with the anomaly, or the mother is older than 40 years old, prenatal diagnosis is suggested, i.e amniocentesis, chorionic villus sampling to check the karyotype of the expected baby.