Cognitive disorder in consanguineous families
COGNITIVE dysfunction (CD) is a more sophisticated term for intellectual disability or mental retardation.
It is a neurodevelopment disability characterized by impaired cognitive functioning; defining a significant sub-average intellectual ability and limitations in at least two or more adaptive skills with the onset before age of 18 years.
Intellectual dysfunction is an overall intelligence quotient (IQ) lowers than 70 and adaptive behaviour is associated with functional deficit in daily-living skills, social and communication skills.
Assuming average IQ of 100 in normal population, the disease is grouped into, on the basis of severity: mild (IQ level 50 to 69); moderate (IQ level 35 to 49); severe (IQ level 20 to 34); and profound (IQ level below 20) (WHO, 1992).
It affects 1-3% of general population and has serious impact on the life of affected individuals, their families and the society as a whole. The prevalence of mild cognitive dysfunction is 85%, that of moderate cognitive dysfunction 10%, whereas only 5% of the patients are classified as severe/profound cognitive dysfunction.
On the basis of associated anomalies, CD can be categorized into syndromic and non-syndromic form.
Syndromic form of CD is accompanied by malformations and dysmorphic features like muscular weakness, skeletal defects etc; whereas non-syndromic forms have no co-morbid features.
It is very tough to differentiate between these two types of CD because the non-syndromic form of the disorder is not so common because CD affects brain that ultimately causes other abnormalities in the patient as well.
Neurodevelopment disorders are among major health concerns in low and middle-income countries due to social and economic hindrance. These disorders account for more than 10% of the Global Burden of Disease across the lifespan.
Pakistan is a country among higher reported rates of childhood intellectual disabilities in the world. The prevalence estimates vary from 19.1/1000 for serious intellectual disability to 65/1000 for mild intellectual disability.
Consanguinity is an important determinant of inherited disorders. Consanguinity is one of the main causes of infant mortality and neurodevelopment disorders in Pakistan. Consanguineous marriages are considered one of the main etiological factors in the high prevalence of severe cognitive dysfunction in Pakistan.
In humans, the high levels of inbreeding are somehow linked to a generally reduced cognitive ability. Consanguineous marriage is defined as the union of two individuals having a common ancestor.
It is estimated that worldwide 10.4% of all marriages occur among relatives, but higher rates of consanguineous marriages have been reported in north and sub-Saharan Africa, the Middle East, and West, Central, and South Asia.
The rate of consanguinity is very high in Pakistan (>60%) with 17–38% first-cousin marriages.
Cognitive dysfunction represents one of the most difficult challenges faced today by clinicians and geneticists due to its extreme heterogeneity.
The extremely heterogeneous causes are contributed by environmental and genetic factors and have been diagnosed in only one half of the cases.
Environmental factors include prenatal exposure of the fetus to toxic substances (toxins, drugs, etc), illness of the mother (e.g. exposure to cytomegalovirus, rubella), premature birth and management after birth.
Genetic factors include chromosomal abnormalities and monogenic defects. Knowledge about monogenic causes has increased significantly in recent years.
Monogenic or single gene defects can be linked to X-chromosome or on autosomes. More than 100 genes have been concerned in X-linked CD until now.
Autosomal linked CD, either due to dominant de novo mutations or recessive gene abnormalities, are apparently most widespread than X-linked CD, and their genetic description is a novel complex task for research purpose.
Recent studies have shown that autosomal recessive cognitive dysfunction (ar-CD) is extremely heterogeneous which is not surprising because about one half of all human genes are expressed in the brain and that is the reason to believe that the number of underlying gene defects will go into thousands. Recessive variant have increased likelihood to spread in consanguineous populations.
There is an urgent need to increase the general public awareness about the inherited disorders. Pakistani communities should be informed about the benefits of genetic analyses in affected families and clans for concerned disorders.
Along these lines, a decline in the frequency of consanguineous marriages has been observed in some countries.
This will be achieved by elevating the levels of education attainments, industrialization, social stratification and an improved economic status of families, much alike the transitions seen in developed countries about health care along with governing policies.
These approaches can provide a clear roadmap to develop strategies in order to address the issues of increasing rates of cognitive dysfunction and other inherited disorders in Pakistan and other countries that have a high consanguinity rate.
—Co-author, Iqra Ghulam Rasool, the University of Veterinary & Animal Sciences Lahore (UVAS).