Genetic Transmission of Diseases

Each cell of human body has 23 pairs of chromosomes. Genes are DNA proteins containing specific set of instructions for our body. Each gene has a specific location on our 23 chromosomes. One copy of each pair of chromosomes  from each of our parents is inherited to our children. 22 pairs of chromosomes are known as autosomes. The 23rd pair is termed sex chromosomes, female having 2 copies of XX chromosomes and male having one copy of X and one copy of Y chromosome.

The genetic factors play role in all health conditions and characteristics. In genetic disorder or inherited diseases, the genetic changes from the parents  are wholly responsible. In mutation, sometimes in a normal parents, there might be spontaneous changes in the gene causing genetic disorder in the child.

The inheritance may be due to single gene disorders or multiple gene disorders.  The single gene disorder may be autosomal dominant or recessive and  X Elinked or recessive.

In dominant disorder, the disease can occur when there are DNA mistakes or in only one of the 2 gene copies. In recessive disorder, both the parents must carry at least one copy of  the defected gene. The children who have both the defected gene are from each parents to cause the disorder. Parents with only one defected gene is symptomless. Consanguineous marriage has more risk of inherited disorders. In autosomal dominant disorder, one defected gene in each cell is sufficient for a  person to be affected. There is 50-50 chance that it will pass on each child. Either parent can transmit the disease tp 50% offsprings. It involve all generations. There is no carrier state. Examples of autosomal dominant disorders are achondroplasia, Marfan’s syndrome, Von Willbrand disease, congenital spherocytosis, tuberous sclerosis, osteogenesis imperfecta.

In autosomal recessive disorders both parents are carriers and must have at least one defected gene in order to produce an infected child. There will be 25% diseased, 25% normal and 50% carrier children. If a carrier marries a  normal person, all the offsprings are either normal or  carrier .Increased risk of consanguinity (marriage among the relative) has increased risk of having diseased children and carrier. Examples of autosomal recessive disorders are  sickle cell disease, thalassemias,  cystic fibrosis, spinal a muscular atrophy , Friederich’s Ataxia, congenital adrenal hyperplasia, phenylketonuria, Wilson’s Disease, glycogen Storage disease, Gaucher’s Disease.

In X-linked dominant disorders, defect in one of the 2 copies in X chromosome is sufficient to cause the disorder. As female has two X chromosomes the occurrence is twice common in female than male, there is 50% risk of both female/male offsprings. All the daughters of an affected father are affected and all the sons  are normal. Examples of X-linked dominant disorders are vitamin D resistant rickets, pseudo-hypo-para-thyroidism, X-linked hypo-phosphatemic rickets.

In X-linked recessive disorders, females are carriers and males are affected. A female carrier’s children are 25% normal daughter, 25% normal daughter, 25% carrier daughter and 255 affected son. Affected males will have only carrier daughters and all the sons will be normal. Examples of X-linked recessive disorders are Douchene muscular dystrophy, haemophilia A (factor VIII) and B (factor IX), nephrogenic diabetes inspidus, glucose 6 – phoshphate dehydrogenase deficiency and color blindness etc..

Heredity is process of passing traits from generation to generation. Multifactorial genetic inheritance or complex or polygenic inheritance disorders are caused by a combination of environmental factors and mutation in multiple genes .Examples are breast cancer, Heart diseases, Hypertension, Alzeihmer’s diseases, arthritis, diabetes and obesity etc.. Vitiligo sometimes run in families suggesting genetic basis.  Though difficult to predict in other family members, about 25-50% of peoples with vitiligo have a relative and approximately 6% have siblings with vitiligo. In schizophrenia, genetic and environmental factors act together and there is a strong genetic component having higher incidence in family members. Cancers, breast cancers, ovarian, colorectal, and prostate cancers are caused by multifactorial inheritance by passing from generation to generation. Alzeihmers disease has 4 to 10  times likely to  have in relatives  if there is  one in parents or brother or sisters. Epilepsy often run in families and genes are a major factor in many epileptic syndromes.  There are other polygenic disorders like neural tube defect, cleft lip, cleft palate, Hirschprung disease, hypertrophic pyloric stenosis etc..

With the advancement of medical sciences, more importance is given in prevention of genetic disorders. The methods used are screening of carriers, newborn screening, folic acid before pregnancy, maternal serum screening, prenatal diagnosis and selective termination of affected foetuses, invasive prenatal testing and genetic counselling.

 

Dr. Shyamkumar Laishram, MD Pediatrics