Question 11#

In a child with flat occiput, Brushfield spots, and simian palmar creases, the most common cause of death is:

A. Cardiac failure

A. The presence of low, flat occiput, Brushfield spots, and simian palmar creases indicates Down’s syndrome. The most common cause of death in children with Down’s syndrome is cardiac failure. Though hypothyroidism is a common accompaniment, this is rarely fatal. Suicide is not a major cause of death in this group. In adults with Down’s syndrome, most of whom obtain surgical correction for major cardiac anomalies at a younger age, leukaemia becomes a major killer.

Reference:

1. Hermon C et al. for the Collaborative Study Group of Genetic Disorders. Mortality and cancer incidence in persons with Down’s syndrome, their parents and siblings. Annals of Human Genetics 2001; 65: 167–176.

Question 12#

A child with low-set ears, polydactyly, and coloboma of the iris is diagnosed to have Patau’s syndrome.

Which of the following chromosomal aberrations explains this presentation?

A. Meiotic non-disjunction

A. Patau syndrome results from aneuploidy of chromosome 13 where three copies are found. This is due to non-disjunction of chromosome 13 during meiosis, mostly in the mother. Similar to Down’s, Patau’s syndrome is associated with increasing maternal age. Patau’s syndrome may also occur as a result of random non-disjunction during early cell division, resulting in a mosaic cell population. Rarely, Patau’s syndrome can result from a translocation that leaves the fetus with three copies of chromosome 13. This is often a balanced translocation where almost no significant clinical changes are seen in the carrier, but this can affect the children of the carrier. In non-translocation-related Patau’s syndrome, the chances of a couple having another child with trisomy 13 is less than 1%. Most fetuses with trisomy 13 die in uterus. If survived, the clinical features include mental retardation, microcephaly and holoprosencephaly, structural eye defects, and congenital cardiac anomalies.

Reference:

1. Patau K et al. Multiple congenital anomaly caused by an extra autosome. Lancet 1960; 1: 790–793.

Question 13#

Heritability is often used to express the genetic contribution in a multifactorial disease.

Which of the following best describes heritability?

A. It refers to the share of genes contributing to a phenotype in an individual patient

C. Heritability is the proportion of variation in a trait that can be attributed to genetic factors. It does not apply to a specific trait in an individual patient; it refers to the variation in the population as a whole. It is not immutable for a specific disease in a population; it will vary with the epidemiological changes in risk and environmental influences in a population, but it can be fixed at a specific time and for a given set of circumstances. Heritability is related to the feasibility of finding a candidate gene for a disease or trait; if a disease has zero heritability in a population, there is no chance of finding a gene. But this does not mean that ‘the higher the heritability, the greater the feasibility of locating the genetic cause’. Heritability can be measured for polygenic disorders even when candidate genes are not known. The phenotypic variation seen in the general population for a particular trait, say height of a person, can be explained by:

1. Total environmental effects—includes both shared and non-shared environmental effects.
2. Total genetic effects—includes both additive genetic effects and dominance effects.

Narrow-sense heritability refers to the proportion of total phenotypic variation that can be attributed to additive genetic variance. The proportion of the total phenotypic variation attributed to total genetic variance is called broad-sense heritability.

Reference:

1. Kendler K. Psychiatric genetics: a methodologic critique. American Journal of Psychiatry 2005; 162: 3–11.

Question 14#

The risk of severe affective disorder in relatives of probands with bipolar affective disorder is:

A. 40%

D. The risk of severe affective disorder in first-degree relatives of probands with bipolar disorder is 19%. The average morbid risk of bipolar disorder itself is 8%, while unipolar depression is around 11% in the first-degree relatives of probands with a bipolar disorder. The risk of severe affective disorders in first-degree relatives of probands with unipolar depression is estimated to be around 10%. Note that the lifetime risk of severe affective illness is about 3 to 5% for unipolar and 1% for bipolar disorders in the general population.

Reference:

1. Scourfield J and McGuffin P. Familial risks and genetic counselling for common psychiatric disorders. Advances in Psychiatric Treatment 1999; 5: 39–45.

Question 15#

Which of the following chromosomal abnormalities results in a phenotype with a cat-like cry and facial dysmorphism?

A. Partial deletion chromosome 5

A. The clinical description in the question fits with cri-du-chat syndrome. This is a result of partial deletion of small arm of chromosome 5. Cri-du-chat syndrome was first described by a French paediatrician, Lejeune, in 1963; he coined the term ‘cri-du-chat’ (cry of the cat). The commonly associated clinical features of cri-du-chat syndrome are:

1. Cat-like cry
2. Dysmorphic facies
3. Profound global learning disability

It is now recognized that this triad does not present in all patients. Restrictive language skills and severely delayed psychomotor development are other notable features.

Reference:

1. Cornish K and Bramble B. Cri du chat syndrome: genotype–phenotype correlations and recommendations for clinical management. Developmental Medicine and Child Neurology 2002; 44: 494–497.