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Introduction to Genetic Disorders

Genetic disorders can be classified into

  1. Mendelian disorder                                
  2. Chromosomal Disorder
  3. Multifactorial inheritance                      
  4. Non classic pattern of inheritance 

A. Mendelian Disorder


Determined primarily by single mutant gene. These disorder show mendilian inheritance pattern than can be classified into-

  1. Autosomal Dominant            
  2. Autosomal Recessive                   
  3. X-linked 

Autosomal Dominant

  1. Manifest in Heterozygous state
  2. Each affected individual has an affected parent
  3. It is characterized by vertical mode of transmission (parent and children affected)
  4. Show variability in clinical expression (variable clinical expression).
  5. Having low penetration
  6. An affected individual has a 50% probability of passing the trait to each offspring (Inheritance 50%)


  1. Dystrophy myotonia            
  2. Osteogenesis Imperfecta              
  3. von willebrand diseaseQ
  4. Marfan syndrome                  
  5. Huntington chorea              
  6. Intermittent Porphyria  
  7. Hereditary spherocytosisQ               
  8. Noonans Syndrome                      
  9. Familial hypercholesterolemiaQ                                       
  10. Adult polycystic kidney
  11. AchondroplasiaQ                       
  12. Neuro Fibromatosis                      
  13. Tuberous Sclerosis 

Autosomal Recessive

  1. Clinically manifest only in Homozygous state
  2. An affected person usually has unaffected parents who each carry a single copy of mutant gene (referred as carrier)
  3. Characterized by horizontal mode of transmission i.e siblings are affected.
  4. Clinical presentation is more uniform
  5. Complete penetration is common.
  6. If both parents are carrier for same autosomal recessive gene the probability for disease in offspring is 25% carrier 50% and normal 25%.


  1. Albinism                                               
  2. B-ThalassemiaQ                              
  3. Cystic fihrosisQ                                   
  4. Deafness                           
  5. Emphy sema (alfa-1 antitrypsin deficiency)                    
  6. Friedrichs ataxia
  7. Gauchers disease                                          
  8. Homocystinuria, haemochromatosis

Sickle cell anemiaQ, phenyl ketonuria, Wilson disease.


X-Linked disorder


The clinical risk and severity of the disease are different for two sexes.

  1. The term X-Linked dominant or X-Linked recessive refer only to the expression of the mutant gene in female.
  2. Absence of male to male (i.e. father to son) transmissionQ.

X-Linked Recessive

  1. Males are affected, females are carrier.
  2. Rarely a female can exhibit an x-linked recessive disorder
    1. She may have turner syndrome (45 × 0)
    2. Testicular feminization syndrome
    3. She may had a mother as a carrier and an affected father
    4. Manifesting heterozygously. This occurs as a result of random inactivation (Lyonization) Q
  3. Characterized by oblique mode of inheritance because occurrence of the trait in sons of normal carrier sister of an affected male (uncle and nephew affected).
  4. Mother who is carrier will have 50% chance, daughter to be carrier and 50% chance her sons to be affected. Q
  5. Affected father will have all daughters (100%) to be carrier and non of the son to be affected. Q


  1. Duchene Muscular dystrophy Q                               
  2. Haemophilia A and B
  3. Glucose 6-phosphate dehydrogenase deficienyQ          
  4. Diabetes Insipidus
  5. Lesch Nyhan syndrome                                
  6. Wiskott Aldrich syndrome
  7. Fabry’s disease                                            
  8. Chronic granulomatous disease
  9. Fragile X Syndrome                                              
  10. Color Blindness. 

X-Linked Dominant

  1. Females are affected twice as often as male. Q
  2. An affected female has 50% probability of transmitting the disorder to her sons or daughter.
  3. An affected male transmits the disorder to all of his daughters and more of his sons.
  4. Phenotype may be more variable and less severe in heterozygous affected female than in hemizygous males
  5. Some rare condition may be inherited as X-Linked dominant traits in which there is lethality in hemizygous male (in utero)
    1. Rett’ s syndromeQ                             
    2. Aicardi syndrome
    3. In continertia pigmertiaQ                 
    4. Goltz syndrome ( focal dermal hypoplasia )

E.g.- Hypophosphastemic Rickets. Q


B. Chromosome disorder

  1. Involve lack, excess or abnormal arrangement of chromosome lead to extra copy of the genome (triploidy), an extra chromosome (trisomy), deletion or duplication of portions of chromosome and other defect.
  2. Chromosomal abnormalities are frequent cause of spontaneous abortion, malformations, mental retardation and tumors.
  3. Trisomy (47 chromosome) is most common chromosome imbalance in early spontaneous abortus followed by monosomy (45 chromosome ) and triploidy (69 chromosome)
  4. The extra or missing chromosomes can he either paternal or maternal in origin and error in segregation of chromosome can occur in the germ line infertilized egg.
  5. Trisomy of every chromosome except chromosome 1 has been observed in spontaneous abortion with increase maternal age
  6. Triploidy is usually the result of dispermy (simultaneous fertilization of an egg by two sperms) 

C. Multifactorial


Disease state is due to additive and interactive effect of one or more genes plus environmental factor. Q

These disorders include most of the common malformation

  1. Neural tube defect                
  2. Cleft lip and palate                
  3. CDH              
  4. Pyloric stenosis 

Common multifactorial disease of adult

  1. Scizopherenia      
  2. Hypertension       
  3. Coronary heart disease
  4. Diabetes Mellitus
  1. There is similar rate of recurrence (2-10%) amongst first degree relative
  2. The risk of recurrence may be greater when the disorder is more severe for example the infant who has a long segment hirschsprung disease has a greater chance of having an affected sibling than the infant who has short segment Hirschsprung’s disease.
  3. Some disorder have sex predilection as indicated by unequal male to female ratio (pyloric stenosis is more common male where as congenital dislocation of the hips is more common in females).
  4. Risk of the son of an affected female with pyloric stenosis is 18% compared with the 5% risk for son of an affected male.

Prenatal diagnostic procedures





Chorionic villus sample (CVS)*



11 weeks

11 weeks

Molecular testing, cytogenetic testing, biochemical assay, intrauterine infection

2-5% fetal loss, limb defects, fetomaternal hemorrhage




15 weeks

16-18 weeks

As above

As above + alfa – fetoprotein

1% fetal loss fetomaternal hemorrhage

Cord blood sample


18 weeks

Cytogenetic, molecular and biochemical testing intrauterine infection

1-3% fetal loss, fetomaternal hemorrhage

* CYS should not be done preferably before 10 weeks of pregnancy. Choice of route is an individual decision. Transabdominal route can be used before 12 weeks also.

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