The document discusses genetic disorders, defined as diseases caused by DNA abnormalities ranging from small gene mutations to chromosome changes. It covers genetic terminology, cell division processes (mitosis and meiosis), genetic testing methods, and various inheritance patterns for genetic disorders, including single gene and chromosomal disorders. Additionally, it describes specific conditions like Down syndrome and Edwards syndrome, their causes, symptoms, diagnostic tests, and treatments.

1. GENETIC DISORDERS
Dr. Smriti Arora
Professor cum Principal
College of Nursing AIIMS Rishikesh
smritiamit@msn.com

2. Introduction
• Genetic disorder is a disease that is caused by an abnormality in an
individual's DNA.
• Abnormalities can range from a small mutation in a single gene to
the addition or subtraction of an entire chromosome or set of
chromosomes.
• A mutation is a permanent change in the DNA sequence of a gene.
• Mutations in a gene's DNA sequence can alter the amino acid
sequence of the protein encoded by the gene.

3. Terminology
• Genetics - study of heredity and its variation
• Gene – basic unit of heredity, located in on
chromosome.
• Chromosome- long continuous strand of DNA that
carries genetic information
• Each somatic cell has 46 chromosomes (23 pairs)
• 22 pairs- autosomes , 1 pair- sex chromosome
• Genotype- specific genetic makeup of the individual,
internally coded inheritable information
• Allelle- alternative versions of a gene at a given point
on chromosome

4. Terminology
• Phenotype- outward characteristics of the individual
• Homozygous- same allelles for a given characteristic
• Heterozygous- different allelles, one from father and
one from mother , of a given characteristic.
• Genome – entire heredity information encoded in the
DNA of an organism

6. Cell division
• Two types- mitosis and meiosis.
• Mitosis is a fundamental process for life. During mitosis, a cell
duplicates all of its contents, including its chromosomes, and splits
to form two identical daughter cells. Because this process is so
critical, the steps of mitosis are carefully controlled by a number of
genes. When mitosis is not regulated correctly, health problems
such as cancer can result.
• Meiosis is the type of cell division that creates egg and sperm cells.
• Meiosis , ensures that humans have the same number of
chromosomes in each generation. It is a two-step process that
reduces the chromosome number by half—from 46 to 23—to form
sperm and egg cells. When the sperm and egg cells unite at
conception, each contributes 23 chromosomes so the resulting
embryo will have the usual 46. Meiosis also allows genetic variation
through a process of DNA shuffling while the cells are dividing.

8. • DNA, is the
molecular basis for
inheritance.
• Each strand of DNA
is a chain of
nucleotides,
matching each other
in the center to form
what look like rungs
on a twisted ladder

9. Nucleotide

13. Human genome project
(1990-2003)
• Coordinated by US department of Energy and
National Institute of Health
• Goals:
– Identify all 20,000-25000 genes in human DNA
– Determine the sequence of 3 million chemical base pairs
that make up human DNA
• Since 2003, when human genome sequencing was
completed, much genetic information and technology
has been introduced into healthcare, requiring nurses to
understand and translate these concepts to patients.

14. Genetic Testing
• Based on fundamental genetic investigations, the causes
of important human diseases are being discovered, and
therapies developed.
• Genetic testing involves examining DNA, the chemical
database that carries instructions for body's
functions.
• Sample - blood or cheek swab sample, samples of
hair, saliva, skin, amniotic fluid or other tissue.
• Eg- molecular tests (gene), chromosomal tests,
biochemical tests (enzymes). For example, low levels
of biotinidase enzyme activity is suggestive of biotinidase
deficiency, which is caused by BTD gene variants.

15. Genetic testing
• Chromosomal tests analyze whole chromosomes or long
lengths of DNA to identify large-scale changes.
• Changes that can be found include an extra or missing
copy of a chromosome (trisomy or monosomy,
respectively), a large piece of a chromosome that is added
(duplicated) or missing (deleted), or rearrangements
(translocations) of segments of chromosomes.
• For example, Williams syndrome is caused by a deletion of
a section of chromosome 7

16. Genetic testing
• Gene expression tests look at which genes are turned
on or off (expressed) in different types of cells. When a
gene is turned on (active), the cell produces a molecule
called mRNA from the instructions in the genes, and the
mRNA molecule is used as a blueprint to make proteins.
• Gene expression tests study the mRNA in cells to
determine which genes are active. Too much activity
(overexpression) or too little activity (underexpression) of
certain genes can be suggestive of particular genetic
disorders, such as many types of cancer.

17. Single Gene
disorder/
Mendelian
inheritance
Non Mendelian
inheritance
Chromosomal
disorders
 Autosomal
dominant
 Autosomal
recessive
 X linked
dominant
 X linked
recessive
 Imprinting
 Mitochondrial
 Non Disjunction
 Structural
changes
Classification of Genetic Disorders

18. Autosomal dominant
• An affected individual carries
the single mutant gene in
heterozygous state on one of
the pair of autosomal
chromosomes.
• Individuals with autosomal
dominant diseases have a 50-
50 chance of passing the
mutant gene and therefore the
disorder onto each of their
children.
• Examples : Huntington disease,
neurofibromatosis,
achondroplasia, and polycystic
kidney disease.

19. Autosomal recessive
• An affected individual carries two copies of mutant
gene in homozygous state.
• An affected person usually has unaffected parents
who each carry a single copy of the mutated gene
(and are referred to as carriers).
• Two unaffected carrier parents have a 25% chance
with each pregnancy of having a male or female
child affected by the disorder and the risk of having
a carrier child is 50%.
• E.g. cystic fibrosis, sickle cell anemia,
phenylketonuria, thalassemia, Tay-Sachs disease,
galactosaemia.

20. X linked dominant
• These disorders are caused by
mutations in genes on the X
chromosomes.
• A woman with an X – Linked
dominant disorder has a 50%
chance of having an affected
daughter or son with each
pregnancy, e.g.
hypophosphatemic rickets.
• The sons of a man with an X –
Linked dominant disorders will
not be affected, and all his
daughters will inherit the
condition.

21. X linked recessive
• This is also caused by mutant gene on
the X – Chromosome.
• In this type of inheritance males are
affected, but females can be carriers.
• The sons of a man with an X – Linked
recessive disorder will not be affected,
and his daughters will carry one copy of
the mutant gene.
• With each pregnancy, a woman with an X
– Linked recessive disorder has a 50%
chance of having daughters who carry
one copy of the mutated gene
• E.g. - hemophilia, color blindness,
Duchenne muscular dystrophy

22. Multifactoral Inheritance
• Most diseases have multifactorial inheritance patterns. As the name implies,
multifactorial conditions are not caused by a single gene, but rather are a
result of interplay between genetic factors and environmental factors.
• Many genetic alterations may predispose individuals to the same disease
(genetic heterogeneity). For instance coronary heart disease risk factors
include high blood pressure, diabetes, and hyperlipidemia. All of those risk
factors have their own genetic and environmental components. Thus
multifactorial inheritance is far more complex than Mendelian inheritance and
is more difficult to trace through pedigrees.
• A combination of genes from both parents and environmental factors produces
the trait.
• Pattern of inheritance is not as predictable as in single gene disorders.
• E.g. congenital disorders: cleft lip, cleft palate, spina bifida, pyloric stenosis,
club foot, congenital hip dysplasia, cardiac defects

23. Non traditional inheritance
patterns
• Mitochondrial inheritance
– Mitochondria are organelles found in the cytoplasm of cells.
– Mitochondria are only inherited from the mother's egg, thus only
females can transmit the trait to offspring, however they pass it
on to all of their offspring.
– The primary function of mitochondria is conversion of molecule
into usable energy. Thus many diseases transmitted by
mitochondrial inheritance affect organs with high-energy use
such as the heart, skeletal muscle, liver, and kidneys.
– Inherited almost exclusively from mother.
– E.g. – Kearns Sayre syndrome, Leber’s hereditary optic
neuropathy

25. • Genomic imprinting:
Even though both parents contribute equally to the genetic
content of their offspring, a developmental process called
genomic imprinting sometimes leads to the exclusive
expression of specific genes from only one parent.
– E.g. - Prader Willi syndrome, Angelman syndrome, Beckwith-
Wiedemann syndrome

26. Chromosomal
abnormalities

27. Chromosomal
abnormalities
• Chromosome diseases are genetic diseases where a large
part of the genetic code has been disrupted.
• Chromosomes are long sequences of DNA that contain
hundreds or thousands of genes.
• Every person has 2 copies of each of the 23
chromosomes, called chromosomes 1..22 and the 23rd is
the sex chromosome, which is either X and Y.
• Men are XY and women are XX in the 23rd chromosome
pair.

28. Chromosomal
abnormalities
• Chromosomal diseases arise from huge errors in
the DNA that result from
– having extra chromosomes,
– large missing sequences, or
– other major errors.
• These are usually caused by a random physical
error during reproduction and are not inherited
diseases.

29. • Nondisjunction
– abnormal number of autosomal chromosomes when
chromosomes fail to separate during replication.
– 2n – 1 = monosomic
– 2n + 1 = trisomic
• Examples
– Down's -- trisomy 21 mean life expectancy 17 years. Short in
stature, round face and mental retardation
– Patau's -- trisomy 13 mean life expectancy 130 days
– Edward's --- trisomy 18 mean life expectancy a few weeks

30. • Structural Changes in Chromosomes
– Inversion – occurs when a chromosome segment turns
around 180 degrees.
– Translocation – is movement of chromosomal segments to
another non-homologous chromosome
– Deletion – occurs when a portion of the chromosome
breaks off.
– Duplication – when a portion of a chromosome repeats
itself.

31. Down’s Syndrome
• also called Trisomy 21, is a condition in which extra
genetic material causes delays in the way a child
develops, both mentally and physically. It affects about 1
in every 800 babies.
• Normally, at the time of conception a baby inherits
genetic information from its parents in the form of 46
chromosomes: 23 from the mother and 23 from the
father.
• In most cases of Down syndrome, a child gets an extra
chromosome 21 — for a total of 47 chromosomes instead
of 46. It's this extra genetic material that causes the
physical features and developmental delays associated
with DS.

33. Causes
• In most cases, Down syndrome occurs when there is an
extra copy of chromosome 21.
• This form of Down syndrome is called Trisomy 21.
• The extra chromosome causes problems with the way the
body and brain develop.
• Down syndrome is the most common single cause of
human birth defects.

35. Child with Down syndrome
Note :
• up-slanting
palpebral fissures,
• bilateral epicanthal
folds,
• a small nose with
flat nasal bridge,
• open mouth with
tendency for tongue
protrusion, and
• small ears with
overfolded helix.

36. • Characteristic small
ear with overfolded
helix.

37. Symptoms
• vary from person to person and can range from mild to
severe.
• widely recognized characteristic appearance.
• The head may be smaller than normal and abnormally
shaped. For example, the head may be round with a flat area
on the back.
• The inner corner of the eyes may be rounded instead of
pointed.
• Common physical signs include:
– Decreased muscle tone at birth
– Excessive skin at the nape of the neck
– Flattened nose
– Separated sutures

38. Cont…
• Single crease in the palm of the hand
• Small ears
• Small mouth
• Upward slanting eyes
• Wide, short hands with short fingers
• White spots on the colored part of the eye (Brushfield
spots)

39. Diagnostic tests include
Chorionic villus sampling (CVS)
• CVS involves taking a tiny sample of the placenta, either
through the cervix or through a needle inserted in the
abdomen.
• Advantage : it can be performed during the first
trimester, between 8 and 12 weeks.
• Disadvantage : carries a slightly greater risk of
miscarriage as compared with amniocentesis and has
other complications.

40. Cont…
Amniocentesis
• performed between 15 and 20 weeks of pregnancy,
• Involves the removal of a small amount of amniotic fluid
through a needle inserted in the abdomen.
• The cells can then be analyzed for the presence of
chromosomal abnormalities.
• Carries a small risk of complications, such as preterm
labor and miscarriage.

41. Diagnosis
Percutaneous umbilical blood sampling (PUBS)
• Usually performed after 20 weeks,
• This test uses a needle to retrieve a small sample of
blood from the umbilical cord.
• risks are similar to those associated with amniocentesis.

42. Diagnostic test
Karyotyping
• It is a test to examine chromosomes in a sample of
cells, which can help identify genetic problems as the
cause of a disorder or disease.
• Count the number of chromosomes
• Look for structural changes in chromosomes

43. Cont…
• The sample is placed into a special dish and allowed to
grow in the laboratory.
• Cells are later taken from the growing sample and
stained.
• A microscope is used to examine the size, shape, and
number of chromosomes in the cell sample.
• The stained sample is photographed to provide a
karyotype, which shows the arrangement of the
chromosomes.
• Certain abnormalities can be identified through the
number or arrangement of the chromosomes.

44. Screening tests include
Nuchal translucency testing
• This test, performed between 11 and 14 weeks of
pregnancy,
• Uses ultrasound to measure the clear space in the folds
of tissue behind a developing baby's neck.
• Babies with DS and other chromosomal abnormalities
tend to accumulate fluid there, making the space appear
larger.
• This measurement, taken together with the mother's age
and the baby's gestational age, can be used to calculate
the odds that the baby has DS.
• Nuchal translucency testing is usually performed along
with a maternal blood test.

45. Cont…
The triple screen or quadruple screen (also called
the multiple marker test).
• These tests measure the quantities of normal substances
in the mother's blood.
• As the names imply, triple screen tests for three markers
and quadruple screen includes one additional marker
and is more accurate.
• These tests are typically offered between 15 and 18 weeks
of pregnancy.

46. Integrated screen.
• This uses results from first trimester screening tests
(with or without nuchal translucency) and blood tests
with second trimester quad screen to come up with the
most accurate screening results.

47. Cont…
Genetic ultrasound.
• A detailed ultrasound is often performed at 18 to 20
weeks in conjunction with the blood tests, and it checks
the fetus for some of the physical traits abnormalities
associated with Down syndrome.
• Other tests that may be done include:
– Echocardiogram
– ECG
– X-rays of the chest and gastrointestinal tract

48. Treatment
• No specific treatment
• Gastrointestinal blockage: may need major surgery
immediately after birth.
• Certain heart defects : surgery
• Special education and training is offered in most communities
for children with delays in mental development.
– Speech therapy : help improve language skills.
– Physical therapy : to teach movement skills.
• closely screen for eye problems, hearing loss, thyroid disease,
and other medical conditions associated with the syndrome.
• Support Groups
– National Down Syndrome Society - www.ndss.org
– National Down Syndrome Congress -- www.ndsccenter.org

49. Prognosis
• Persons with Down syndrome are living longer than ever
before. Many live independent and productive lives, well
into adulthood.
• About half of children with Down syndrome are born
with heart problems, including ASD and VSD. Heart
problems may lead to early death.
• Persons with Down syndrome have an increased risk for
certain types of leukemia, which can also cause early
death.
• The level of mental retardation varies from patient to
patient, but is usually moderate. Adults with Down
syndrome have an increased risk for dementia

50. Complications
• Airway blockage during sleep
• Compression injury of the spinal cord
• Eye problems
• Frequent ear infections and increased risk of other infections
• Hearing loss
• Heart problems
• Gastrointestinal blockage
• Weakness of the back bones at the top of the neck

51. Edwards Syndrome
• In Trisomy 18 (Edwards syndrome), there is an extra
chromosome with the 18th pair.
• Like Trisomy 21 (Down syndrome), Trisomy 18 affects all
systems of the body and causes distinct facial features.
• It is estimated to occur in 1 in 6,000-8,000 live births.
Unfortunately, about 95% of fetuses die before birth, so
the actual incidence of the disorder may be higher.
• Of those born, approximately 80% are females.
• Trisomy 18 affects individuals of all ethnic backgrounds.

56. Symptoms
Trisomy 18 severely affects all organ systems of the body.
Symptoms may include:
• Nervous system & brain - mental retardation and delayed
development (100% of individuals), high muscle tone, seizures,
and physical malformations such as brain defects
• Head and face - small head (microcephaly), small eyes, wide-
set eyes, epicanthal folds, small lower jaw
• Heart - congenital heart defects (90% of individuals) such as
VSD and valve defects
• Bones - severe growth retardation, clenched hands with 2nd &
5th fingers on top of the others, other defects of the hands &
feet
• Malformations of digestive tract, urinary tract, & genitals

57. Cont…
• Patient find difficulty in growth.
• They face difficulty in feeding and breathing.
• Mental retardation
• Polyhydramnios and small placenta.
• Small head, small mouth and small jaw.
• Widely-spaced eyes and upturned nose.
• Underdeveloped thumb and nails or may be absent.
• Kidney malformations
• Heart defects.

58. Symptoms
• Crossed legs
• Malformed kidney
• Affected baby may have umbilical or inguinal hernia
• Abnormal ears
• Coloboma (hole) of iris and short sternum
• Short breastbone, Discomfort in the bowels.

59. Diagnosis
• The physical appearance of the child at birth will point
towards Trisomy 18.
• Prenatal ultrasound can detect abnormalities in the fetus.
• Genetic testing by amniocentesis before birth or blood test
after birth can confirm the diagnosis.
• Ultrasounds of the heart and abdomen can detect
abnormalities
• X -rays of the skeleton

60. Treatment
• Medical
– supportive, and
– focuses on providing nutrition,
– treating infections, and
– managing heart problems.
• During the first months of life, infants with Trisomy 18 require
skilled medical care. Due to the complex medical problems,
including heart defects and overwhelming infections, infants
have a 5% chance of surviving to age 1 year.
• Advances in medical care over time will, in the future, help
more infants with Trisomy 18 live into childhood and beyond.

61. Cont…
Treatment is associated with symptoms:
• Babies dysphagia clinic or feeding specialist is essential for the feeding
problem and for other difficulties G-tube is required.
• Parents of baby with low weight gain due to heart defects may consult
with nutritionist.
• A stool softener medication is useful to reduce irritation of bowel in
children.
• Hearing aides and glasses is helpful for those who have hearing and
visual problem.
• Physical and occupational therapy is useful to increase motor skill.
• Anti-gas medication should be used to treat the problem of gas in the
bowels.
• Surgical treatment may be required for the diseases like spina bifida, and
hydrocephalus.

62. Cri-du-chat Syndrome
• Cri du chat Syndrome is a uncommon
and unusual hereditary disorder which
is caused by a deletion of chromosome
5p.
• Chromosome 5p deletion syndrome; 5p
minus syndrome, Cat cry syndrome,
these are some of the alternate name
of Cri du chat Syndrome.

63. Causes
• It mostly occurs due to deletion of chromosome 5p.
• Deletion of gene known as tert may cause the feature of Cri
du chat Syndrome.
• Cause of deletion of chromosome 5p is not known but various
cases are because of sudden loss of chromosome 5p at the
time of expansion of an egg or sperm.
• Some cases occur due to translocation i.e. parents carrying
reorganization of chromosome.
• Severe mental retardation may also cause this disease but it is
in very rare cases.

64. Symptoms
• Children with Cri du chat do not develop perfectly
• They don't get developed larynx because of which when
they cry it sounds like cat cry therefore it is also called Cat
cry syndrome.
• Babies who have Cri du chat carry different features like
they have small head and round face, wide-set eyes,
downward slant to the eyes and skin tags just in front of
the ear.
• These people do not get perfect birth weight and get slow
growth.

65. Symptoms
• Some children experience heart defects, hearing and visual
problem, and they always face problem in walking and
talking.
• Some people have mental retardation.
• These patient experience fusing of fingers or toes, small jaws
and slow development of motor skills.
• Patient of Cri du chat Syndrome may not survive till
adulthood.

66. Cri -du-chat syndrome.
Note
• the round face with full
cheeks,
• hypertelorism,
• epicanthal folds, and
• apparently low-set ears.

67. Note
• the hypertonicity,
• small and narrow face,
• dropped jaw, and
• open-mouth
expression secondary
to facial laxity.

68. Diagnosis
 Molecular cytogenetic studies using FISH (Fluorescence
in situ hybridization) allow the diagnosis to be made in
patients with very small deletions.
 Chromosome comparative genomic hybridization (CGH)
• Imaging studies
– MRI
– ECHO
 Skeletal radiography
 Developmental testing

69. Karyotyping

70. Surgical Care
• Correction of congenital heart defects may be indicated.
• Medical problems involving minor malformations such as
strabismus and clubfoot may be amenable to surgical
correction.
• Orchiopexy may be necessary in patients with
undescended testes.

71. Treatment
• Care must be taken , it is very helpful. No treatment
survive for fundamental hereditary disorder.
• The child may need gastrostomy tube for feeding.
• Speech therapist should use to improve communication
skills
• Physical therapy is also useful.
• Chronic medical problems such as upper respiratory
tract infections, otitis media, and severe constipation
require appropriate treatment.

72. Mortality/Morbidity
• With contemporary interventions, the chance of survival
to adulthood is possible.
• Currently, the mortality rate of cri-du-chat syndrome is 6-
8% in the overall population.
• Pneumonia, aspiration pneumonia, congenital heart
defects, and respiratory distress syndrome are the most
common causes of death.

73. Summary
• Patterns of inheritance
• Downs syndrome
• Edwards syndrome
• Cri du chat syndrome

74. • Thankyou !