This document discusses genetic disorders, their causes, classification, and examples. It begins by defining genetics and genetic disorders. Genetic disorders can be caused by mutations in one gene (monogenic) or multiple genes (multifactorial). They are classified based on inheritance patterns (autosomal dominant, recessive, X-linked) or chromosome abnormalities (numerical, structural). Examples of common single-gene disorders discussed include cystic fibrosis, sickle cell anemia, and Huntington's disease. Examples of chromosomal disorders include Down syndrome, Edward syndrome, and Turner syndrome. Cancer is also discussed as having both genetic and environmental causes.

1. GENETIC PATTERN OF
COMMON PEDIATRIC DISORDER
HARSHITA
M. SC NURSING

2. GENETICS
Genetics is the study of genes, genetic variation,
and heredity in living organisms.

3. GENETIC DISORDER
A genetic disorder is a genetic problem caused by one or more
abnormalities in the genome, especially a condition that is
present from birth (congenital). Most genetic disorders are quite
rare and affect one person in every several thousands or millions.

4. HOW GENETIC DISORDER IS CAUSED
A genetic disorder is a disease caused in whole or in part by a
change in the DNA sequence away from the normal sequence.
Genetic disorders can be caused by a mutation in one gene
(monogenic disorder), by mutations in multiple genes
(multifactorial inheritance disorder), by a combination of gene
mutations and environmental factors, or by damage to
chromosomes (changes in the number or structure of entire
chromosomes, the structures that carry genes).

5. CLASSIFICATION OF GENETIC DISORDERS
A. Genetic disorders due to traditional modes of inheritance.
Mendelian disorders: (Single gene)
• Autosomal dominant (AD)
• Autosomal recessive (AR)
• X-linked recessive (XLR)
• X-linked dominant (XLD)

6. CLASSIFICATION OF GENETIC DISORDERS
• Chromosomal disorders:
• Numerical abnormalities
• Structural abnormalities
• Multifactorial disorders
• Somatic cell mutations

7. CLASSIFICATION OF GENETIC DISORDERS
B. Genetic disorders due to non-traditional modes of inheritance.
• Mosaicism
• Genomic imprinting
• Uniparental disomy (UPD)
• Inheritance of unstable mutations
• Cytoplasmic/mitochondrial inheritance

8. MENDELIAN (SINGLE GENE) DISORDERS
• When a certain gene is known to cause a disease, it is a single
gene disorder or a Mendelian disorder.
• Disorders caused by a defect in a single gene follow the
patterns of inheritance described by Mendel. Risks within an
affected family are usually high and are calculated by knowing
the mode of inheritance and details of the family pedigree

9. AUTOSOMAL DOMINANT DISORDERS
• Generally, the autosomal dominant mutations caused faults in
the synthesis of structural or non-enzyme proteins.
• These disorders manifest even if only one of the alleles of the
normal gene is affected

11. AUTOSOMAL RECESSIVE DISORDERS
• Autosomal recessive disorders manifest only in homozygous
states, i.e. both the alleles are mutant genes.
• Generally autosomal recessive mutation affect synthesis of
enzyme proteins, leading to inborn error of metabolism.

13. X-LINKED RECESSIVE DISORDERS
• Males have an X and shorter Y chromosome. There may be no
corresponding locus or mutant allele of the X chromosome on
the shorter Y chromosome. The mutant recessive gene on X
chromosome, therefore expresses as a clinical disorder in male
child.
• In X-linked recessive conditions only males are affected as
there is no corresponding allele. All his daughters will be
carriers as they receive abnormal X from father.

15. X-LINKED DOMINANT DISORDERS
These disorders manifest even in XX females as it is an
dominant gene. The gene is transmitted in families in the same
way as X-linked recessive genes, giving rise to an excess of
affected females.
• In some disorders the condition is lethal in hemizygous males.
In this case there will be fewer males than expected in the
family, all of whom will be healthy, and an excess of females,
half of whom will be affected.
• There is no male to male transmission in this pattern of
inheritance

17. CHROMOSOMAL DISORDERS
• Chromosomal abnormalities are generally sporadic and
therefore, the risk of their recurrence in the offspring is low.
There are two type of chromosomal abnormalities numerical
and structural

18. NUMERICAL DISORDERS
This is 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.).

20. STRUCTURAL ABNORMALITIES
When the chromosome's structure is altered, this can take several forms:
Deletions: A portion of the chromosome is missing or deleted. Known
disorders in humans include Wolf-Hirschhorn syndrome, which is caused by
partial deletion of the short arm of chromosome 4; and Jacobsen syndrome,
also called the terminal 11q deletion disorder.
Duplications: A portion of the chromosome is duplicated, resulting in extra
genetic material. Known human disorders include Charcot-Marie-Tooth
disease type 1A, which may be caused by duplication of the gene encoding
peripheral myelin protein 22 (PMP22) on chromosome 17.

21. STRUCTURAL ABNORMALITIES
• Translocations: A portion of one chromosome is transferred to
another chromosome. There are two main types of translocations:
• Reciprocal translocation: Segments from two different chromosomes
have been exchanged.
• Robertsonian translocation: An entire chromosome has attached to
another at the centromere - in humans these only occur with
chromosomes 13, 14, 15, 21, and 22.
• Inversions: A portion of the chromosome has broken off, turned
upside down, and reattached, therefore the genetic material is
inverted.

22. STRUCTURAL ABNORMALITIES
• Insertions: A portion of one chromosome has been deleted
from its normal place and inserted into another chromosome.
• Rings: A portion of a chromosome has broken off and formed a
circle or ring. This can happen with or without loss of genetic
material.
• Isochromosome: Formed by the mirror image copy of a
chromosome segment including the centromere

23. ABNORMALITIES

24. MULTIFACTORIAL DISORDERS
Inheritance and expression of a phenotype being
determined by multiple gene at different loci and
the effects of the genes are cumulative, with each
gene contributing a small amount to the final
expressed phenotype aided by certain
environmental factors.

25. SOMATIC CELL MUTATIONS
Some cancers can be inherited as simple Mendelian
traits, with clear patterns of transmission, this is the
exception rather than the rule. Even though most
cancers involve quite substantial changes in the
genetic material, such mutations are somatic and
there is no risk to further generations.

26. MOSAICISM
• Somatic mosaicism is the term used to describe the finding of
two different cell lines in one individual that are derived from a
single zygote (i.e. coming from a single egg and sperm). It
occurs as a postzygotic event (after fertilization).
• The mosaicism may be for (i) chromosomal abnormalities or (ii)
single gene mutations.

27. MOSAICISM
• Chromosomal Mosaicism
It has been recognized in cultured lymphocytes of patients with
chromosomal aneuploidy syndromes.
• Single Gene Mosaicism
Somatic mosaicism for single gene mutations.

28. MOSAICISM
• Germline Mosaicism
Germline mosaicism refers to the presence of mosaicism in the
germ cells found in the gonads. The mosaicism may be for
chromosomal abnormality or a single gene mutation. Germ line
mosaicism has been found in Duchenne muscular dystrophy,
chronic granulomatous disease and osteogenesis imperfecta.

29. GENOMIC IMPRINTING
During the last decade, several new mechanisms of genetic
inheritances have been recognized and one such is genomic
imprinting.

30. UNIPARENTAL DISOMY
An individual inherits a pair of homologous chromosomes, one
from the father and the other from the mother. Recent DNA
technology has revealed that an individual may inherit both
homologous chromosomes from only one of his parents and this
situation is called as uniparental disomy.

32. MITOCHONDRIAL INHERITANCE
Mitochondria are intracellular organelles which are ubiquitous in
eukaryotes and are essential for survival

34. DOWN SYNDROME
• Down syndrome, the most
common chromosomal
condition that results in
intellectual disabilities, is
associated with an extra
chromosome on
chromosome 21.

35. DOWN
SYNDROME

37. EDWARD
SYNDROME
• Edward syndrome also
known as trisomy 18, is a
rare but serious genetic
condition that causes a wide
range of severe medical
problems

38. SYMPTOMS
• low birthweight
• a small, abnormally shaped head
• a small jaw and mouth
• long fingers that overlap, with underdeveloped thumbs and clenched fists
• low-set ears
• smooth feet with rounded soles
• a cleft lip and palate
• an exomphalos (where the intestines are held in a sac outside the tummy)

40. PATAU SYNDROME
Patau syndrome is a syndrome
caused by a chromosomal
abnormality, in which some or
all of the cells of the body
contain extra genetic material
from chromosome 13. The
extra genetic material disrupts
normal development, causing
multiple and complex organ
defects.

42. KLIFENTER SYNDROME
Klinefelter syndrome is a genetic
disorder that affects males. Klinefelter
syndrome occurs when a boy is born
with one or more extra X
chromosomes.

44. TURNER
SYNDROME
Turner syndrome is a
genetic disorder that
affects about 1 in every
2,000 baby girls and only
affects females. A girl with
Turner syndrome only has
one normal X sex
chromosome, rather than
the usual two (XX).
This chromosome variation
happens randomly when
the baby is conceived in
the womb. It is not linked
to the mother's age.

46. THALASSAEMIA
Thalassaemia is a blood
related genetic disorder which
involve the absence of or
errors in genes responsible for
production of haemoglobin, a
protein present in the red
blood cells.

48. SICKLE CELL ANEMIA
• Sickle-cell anemia is a blood
related disorder that affects the
haemoglobin molecule, and
causes the entire blood cell to
change shape under stressed
conditions. In sickle cell anaemia,
the haemoglobin molecule is
defective. After haemoglobin
molecules give up their oxygen,
some may cluster together and
form long, rod-like structures
which become stiff and assume
sickle shape.

49. HAEMOPHILIA
• Haemophilia is a hereditary bleeding disorder, in which there is
a partial or total lack of an essential blood clotting factor. It is a
lifelong disorder, that results in excessive bleeding, and many
times spontaneous bleeding, which, very often , is internal.
Haemophilia A is the most common form, referred to as
classical haemophilia. It is the result of a deficiency in clotting
factor 8, while haemophilia B (Christmas Disease) is a
deficiency in clotting factor 9. This illness is a sex-linked
recessive disorder.

51. CYSTIC FIBROSIS
Cystic Fibrosis is a genetic
disorder that affects the
respiratory, digestive and
reproductive systems
involving the production of
abnormally thick mucus
linings in the lungs and can
lead to fatal lung
infections. The disease can
also result in various
obstructions of the
pancreas, hindering
digestion.

53. TAY SACHS DISEASE
Tay-Sachs disease is a fatal genetic disorder in which harmful
quantities of a fatty substance called Ganglioside GM2
accumulate in the nerve cells in the brain. This is caused by a
decrease in the functioning of the Hexosaminidase A enzyme.

55. FRAGILE X
SYNDROME
The Fragile X syndrome is
caused by a "fragile" site at
the end of the long arm of
the X-chromosome. It is a
genetic disorder that
manifests itself through a
complex range of
behavioural and cognitive
phenotypes.

56. HUNTINGTON'S DISEASE
Huntington’s disease is a degenerative brain disorder, in which
afflicted individuals lose their ability to walk, talk, think, and
reason. They easily become depressed, and lose their short-term
memory capacity. They may also experience a lack of
concentration and focus

57. CANCER
• Cell undergoes in the process of malignant transformation.
• This take over 20 years or more.
• The mutation of critical genes, including supressor genes, oncogenes
and genes involved in DNA repair, leads to genetic instability and to
progressive loss of differentiation.
• Tumours enlarge because cancer cells lack the ability to balance cell
division by cell death (apoptosis) and by forming their own vascular
system (angiogenesis) .

58. CANCER
• The transformed cells lose their ability to interact with each
other and exhibit uncontrolled growth, invade neighbouring
tissues and eventually spread through the blood stream or the
lymphatic system to distant organs.

59. DIABETES
Diabetes is a disease in which the body does not produce or
properly use insulin. Insulin is a hormone that is needed to
convert sugar, starches and other food into energy needed for
daily life. The cause of diabetes continues to be a mystery,
although both genetics and environmental factors such as
obesity and lack of exercise appear to play roles. There are three
major classes of diabetes
• Type 1 diabetes
• Type 2 diabetes

60. CARDIOVASCULAR DISEASE
Cardiovascular diseases (CVD) include coronary heart disease,
cerebrovascular disease, heart failure, rheumatic heart disease
and congenital heart disease.
The major risk factors associated with cardiovascular diseases
are cigarette smoking, unhealthy diet, physical inactivity,
hypertension, diabetes and high blood cholesterol.
CVD may also result from a variety of genetic causes, including
single-gene mutations, the interaction of multiple genes and
environmental factors.

61. ASTHMA
Asthma is a disease in which the airways become blocked or narrowed.
These effects are usually temporary, but they cause shortness of
breath, breathing trouble, and other symptoms. When encountering a
triggering particle, there is an inflammation of the linings, a
constriction of the airways and mucous production. This results in
difficulty in breathing, and may even block the airways completely. If
an asthma episode is severe, a person may need emergency treatment
to restore normal breathing. An asthma episode is triggered by things
in the environment. These triggers vary from person to person, but
common ones include cold air; exercise; allergens such as dust mites,
mould, pollen, Cigarette smoke, animal dander or cockroach debris;
and some types of viral infections.

62. MANAGEMENT
(i) Restriction of potentially toxic environmental agents,
(ii) Replacement of missing gene product, deranged organ or
even gene itself
(iii)Removal of either toxic substances of organs
(iv)Metabolic manipulation
(v) Surgical management.

63. RESTRICTION
(a) Phenylketonuria – phenylalanine should be restricted in the
diet,
b) Galactosemia – galactose should be eliminated from the diet
early in life. If prenatal diagnosis is made, the mother should not
drink milk in pregnancy,
(c) G-6-PD deficiency – primaquine, sulpha drugs and fava
beans should be restricted,

64. REPLACEMENT
• Examples for the replacement mode of treatment are:
• a. Hemophilia A and B: The treatment aims at replacement of factor VIII and factor IX by transfusion
respectively.
• b. Diabetes mellitus: Insulin is the agent replaced.
• c. Alpha-1 antitrypsin deficiency: Can be successfully treated by replacement with recombinant alpha-
1 antitrypsin.
• d. Congenital adrenal hyperplasia: The agents replaced are cortisone and aldosterone.
• e. Cystinosis Kidney transplantation.
• f. Adenosine deaminase deficiency: Bone marrow transplantation or somatic cell gene therapy.
• g. Familial hypercholesterolemia: Liver transplantation

65. REMOVAL
• The examples are:
(a) Wilson’s disease: It is an autosomal recessive disorder characterized
by accumulation of copper in various organs like the liver, brain and
kidneys. The copper can be effectively chelated by oral administration
of penicillamine;
(b) Hemochromatosis: The excess iron stores are removed by repeated
phlebotomy;
(c) Familial Polyposis coli: Colectomy is advised to prevent carcinoma
of colon, which develops during the fourth decade of life.

66. METABOLIC MANUPULATION
• Metabolic manipulation can correct certain types of disorders which
are: (a) Neural tube defects: Periconceptional folic acid therapy has
shown to prevent neural tube defects
(b) Homocystinuria: Classic homocystinuria is due to deficiency of
cystathionine synthetase. Among these, 40 percent of patients respond
to high doses of vitamin B6.
(c) Crigler-Najjar syndrome type II: These patients benefit by oral
phenobarbitone administration which induces hepatic glucuronyl
transferase activity;

67. SURGICAL MANAGEMENT
• Surgical management can be considered in certain cases like:
• (a) Congenital adrenal hyperplasia: Clitoroplasty and vaginal
reconstruction surgery;
• (b) Marfan syndrome: Surgery for aortic dilatation;
• (c) Hydrocephalus: Shunt surgery;
• (d) Obstructive uropathy: Intrauterine shunt or correction;
• (e) Diaphragmatic hernia: Repair

68. GENE THERAPY

69. GENETIC ENGINEERING