① ABSTRACT:
Chromosome disorders are abnormalities that occur in the number or structure of chromosomes,
which are the thread-like structures that contain our genetic material. These disorders can affect
individuals of any age, race, or gender and may result from a variety of causes. Some of the most
common chromosome disorders include Down syndrome, Turner syndrome, and Klinefelter
syndrome.
Down syndrome is caused by an extra copy of chromosome 21, which leads to intellectual
disability, distinct facial features, and a range of health conditions such as heart defects and
gastrointestinal problems. Turner syndrome occurs when a female is missing all or part of one of
her X chromosomes, leading to short stature, infertility, and other health issues. Klinefelter
syndrome is characterized by the presence of an extra X chromosome in males, which can lead to
infertility, learning difficulties, and other physical and psychological symptoms.
Chromosome disorders can occur due to a variety of factors, including errors during cell division,
exposure to certain chemicals or radiation, and genetic mutations. In some cases, these disorders
may be inherited from one or both parents. Diagnosis of chromosome disorders typically involves
genetic testing, which can include blood tests, imaging studies, and other diagnostic tools.
Treatment for chromosome disorders typically involves medical management and supportive care,
which may include medications, surgery, and other interventions as needed. While chromosome
disorders cannot be cured, early detection and intervention can improve outcomes and quality of
life for affected individuals. Support from family, friends, and healthcare providers can also play an
important role in helping individuals with chromosome disorders manage their symptoms and live
fulfilling lives.
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② CHROMOSOME DISORDER:
• A chromosome disorder results from a change in the number or structure of chromosomes.
• Each of our chromosomes has a characteristic structure.
• Historically, scientists have used a staining technique that colours the chromosomes into a
banding pattern.
• These banding patterns make each of our individual chromosomes easier to identify, like a
map.
• A set of chromosomes, as seen under a microscope, is known as a karyotype.
• Any deviation from the normal karyotype is known as a chromosome abnormality.
• While some chromosome abnormalities are harmless, some are associated with clinical
disorders.
• Half of all spontaneous abortions are due to chromosome abnormalities.
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③ NUMERICAL ABNORMALITIES:
Chromosomal disorders are due to the change in the number of chromosomes present. This can
be categorized into various types:
• Aneuploidy: loss or gain of a chromosome. This happens due to non-disjunction of
chromatids when chromatids fail to separate during cell division. This results in one gamete
having two copies of one chromosome and the other having no chromosome.
• Trisomy: The cell has one extra chromosome (2n+1)
• Monosomy: The cell has one chromosome less (2n-1)
• Aneuploidy can be due to nondisjunction of autosomes i.e., chromosomes 1-22 or sex
chromosomes.
• Chromosomal disorders due to aneuploidy: This is the cause of most of the genetically
inherited disorders and abortion during pregnancy.
• Euploidy: Loss or gain of the whole set of chromosomes. Mostly occurs in plants.
• Haploid: Loss of one set of chromosomes, i.e., ‘n’ number of chromosomes
• Polyploid: Addition of one or more set of chromosomes, e.g., ‘3n (triploid)’, ‘6n (hexaploid)’
etc.
TABLE: Major numerical abnormalities that survive to term
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IMAGE: Karyotype images showing different numerical abnormalities
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④ STRUCTURAL ABNORMALITIES:
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This is when large sections of DNA are missing from or are added to a chromosome.
Structural abnormalities can take several forms.
Deletion: a mutation causing part of the chromosome to be missing.
Duplication: a mutation causing part of the chromosome to be repeated, resulting in extra genetic
material.
Tandem duplication, where the duplicated region is present side by side (ABCDEF→ABCDEDEF).
Reverse tandem, here duplicated region is just reverse of the normal sequence
(ABCDEF→ABCDEEDF).
Displaced duplication, here duplicated region is not situated adjacent to the normal sequence.
Transposed duplication, duplicated part becomes attached to a non-homologous chromosome.
Extra-chromosomal duplication, here duplicated part acts as an independent chromosome in the
presence of centromere.
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Translocation: a mutation causing one portion of a chromosome to be moved to a different part of
the chromosome (intrachromosomal) or to a different chromosome altogether (interchromosomal).
There are two key types:
• Reciprocal: segments from two different chromosomes are exchanged.
• Robertsonian: an entire chromosome attaches to another.
Inversion: a mutation resulting in a portion of a chromosome being in the opposite orientation
(inverted).
Ring: when a portion of a chromosome has broken off and formed a circle or ring.
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Balanced structural abnormalities involve the rearrangement of genetic material but with no overall
gain or loss. For example, inversions and translocations.
Balanced structural abnormalities can have an immediate effect, but the major consequence is the
production of eggs or sperm with incomplete or partially duplicated sets of chromosomes.
Unbalanced structural abnormalities involve genetic material being gained or lost.
Even tiny unbalanced structural abnormalities can affect many genes and, consequently, have
severe effects on the individual.
TABLE: Unbalanced structural abnormalities
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⑤ HOW CHROMOSOMAL ABNORMALITIES OCCUR:
Chromosome abnormalities usually occur when there is an error in cell division resulting in cells
with too few or too many copies of a chromosome.
Most chromosome abnormalities originate in egg or sperm (gametes) but some happen during
embryo development or are inherited from a parent.
Chromosome abnormalities that originate in the gametes are present in every cell of the body.
Normally during the formation of gametes, the two pairs of chromosomes (one from the mother
and one from the father), separate in a process called meiosis. This results in just one copy of
each chromosome in the gametes (as opposed to the two copies found in the other cells of the
body).
Errors in this separation process led to the formation of gametes with incomplete sets of
chromosomes or additional whole or parts of chromosomes. This is known as meiotic
nondisjunction.
Other factors that can increase the risk of chromosome abnormalities include maternal age (the
frequency of meiotic nondisjunction increases with maternal age) and environmental factors such
as exposure to certain drugs.
Even tiny changes in the chromosome structure can affect multiple genes and have significant
effects.
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⑥ SOME CHROMOSOMAL ABNORMALITIES:
Some examples of chromosomal abnormalities are:
➊ Wolf-Hirschhorn Syndrome
➋ Jacobsen Syndrome
➌ Angelman Syndrome
➍ Turner Syndrome
➎ 22q11.2 Deletion Syndrome
➏ Triple X Syndrome
➐ Williams Syndrome
➑ Cri Du Chat Syndrome
➒ Trisomy 13
➓ Cat Eye Syndrome
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Wolf-Hirschhorn Syndrome:
Description: Wolf-Hirschhorn syndrome is caused by the deletion of the distal short arm of
chromosome 4. The disorder’s major features include a characteristic facial appearance, delayed
growth and development, intellectual disability, and seizures.
➡️ Signs and symptoms:
The most common characteristics include a distinct craniofacial phenotype (microcephaly,
micrognathia, short philtrum, prominent glabella, ocular hypertelorism, dysplastic ears and
periauricular tags), growth restriction, intellectual disability, muscle hypotonia, seizures, and
congenital heart defects. Less common characteristics include hypospadias, colobomata of the
iris, renal anomalies, and deafness. Antibody deficiencies are also common, including common
variable immunodeficiency and IgA deficiency. T-cell immunity is normal.
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Jacobsen Syndrome:
Description: Jacobsen syndrome, also known as 11q deletion disorder, results from a loss of
genetic material from the end of the long arm of chromosome. Signs and symptoms of this
condition vary, but most individuals experience delayed development in motor skills and speech,
cognitive impairments, learning difficulties, and some behavioral problems.
➡️ Signs and symptoms:
• Mild to severe intellectual disabilities
• Low platelets (thrombocytopenia)
• Facial/skeletal (dysplasia)
• Wide-set eyes caused by trigonocephaly
• Folding of the skin near the eye (epicanthus)
• Short, upturned nose (anteverted nostrils)
• Thin lips that curve inward
• Displaced receding chin (retrognathia)
• Low-set, misshapen ears
• Permanent upward curvature of the pinkie and ring fingers (camptodactyly)
• Large great toes/Hammer toes
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Angelman Syndrome:
Description: Angelman syndrome (AS) is an example of genomic imprinting, where the deletion or
inactivation of genes on the maternally inherited chromosome 15 causes the paternal copy, which
may be of normal sequence, to be imprinted and silenced. AS is characterized by intellectual and
developmental delays, sleep disturbances, seizures, and jerky movements, but also frequent
laughter or smiling and usually have a happy demeanor.
➡️ Signs and symptoms:
The following text lists signs and symptoms of Angelman syndrome and their relative frequency in
affected individuals.
Consistent (100%)
• Developmental delay, functionally severe
• Speech impairment, no or minimal use of words; receptive and non-verbal communication
skills higher than verbal ones
• Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
• Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy
demeanor; easily excitable personality, often with hand flapping movements; hypermotoric
behavior; short attention span
Frequent (more than 80%)
• Delayed, disproportionate growth in head circumference, usually resulting in microcephaly
(absolute or relative) by age 2
• Seizures, onset usually less than 3 years of age
• Abnormal EEG, characteristic pattern with large amplitude slow-spike waves
Associated (20–80%)
• Strabismus
• Hypopigmented skin and eyes
• Tongue thrusting; suck/swallowing disorders
• Hyperactive tendon reflexes
• Feeding problems during infancy
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• Uplifted, flexed arms while walking
• Prominent mandible
• Increased sensitivity to heat
• Wide mouth, wide-spaced teeth
• Sleep disturbance
• Frequent drooling, protruding tongue
• Attraction to/fascination with water
• Excessive chewing/mouthing behaviors
• Flat back of head
• Smooth palms
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Turner Syndrome:
Description: Turner syndrome (TS) occurs when one of the two X chromosomes in females is
either missing or incomplete. The most common symptoms are short stature and gonadal
dysgenesis, which can cause incomplete sexual development and ovarian failure and infertility. As
of right now, there is no known cause of TS.
➡️ Signs and symptoms:
Of the following common symptoms of Turner syndrome, an individual may have any combination
of symptoms and is unlikely to have all symptoms.
• Short stature
• Lymphedema (swelling) of the hands and feet of a newborn
• Broad chest (shield chest) and widely spaced nipples
• Low posterior hairline
• Low-set ears
• Reproductive sterility
• Rudimentary ovaries gonadal streak (underdeveloped gonadal structures that later become
fibrotic)
• Amenorrhoea, the absence of a menstrual period
• Increased weight, obesity
• Shortened metacarpal IV
• Small fingernails
• Characteristic facial features
• Webbed neck from cystic hygroma in infancy
• Aortic valve stenosis
• Coarctation of the aorta
• Bicuspid aortic valve (most common cardiac problem)
• Horseshoe kidney
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• Visual impairments – sclera, cornea, glaucoma, etc.
• Ear infections and hearing loss
• High waist-to-hip ratio (the hips are not much bigger than the waist)
• Attention deficit hyperactivity disorder (problems with concentration, memory, attention with
hyperactivity seen mostly in childhood and adolescence)
• Nonverbal learning disability (problems with math, social skills, and spatial relations)
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22q11.2 Deletion Syndrome:
Description: 22q11.2 deletion syndrome is caused by the deletion of a small piece of chromosome
22 near the middle of the chromosome. Because signs and symptoms of 22q11.2 deletion
syndrome are varied, different groupings of symptoms were once described as completely
separate conditions, named DiGeorge syndrome, velocardiofacial syndrome, and conotruncal
anomaly face syndrome.
➡️ Signs and symptoms:
The features of this syndrome vary widely, even among members of the same family, and affect
many parts of the body. Characteristic signs and symptoms may include birth defects such as
congenital heart disease, defects in the palate, most commonly related to neuromuscular
problems with closure (velopharyngeal insufficiency, or VPI), learning disabilities, mild differences
in facial features, and recurrent infections. Infections are common in children due to problems with
the immune system's T-cell-mediated response that in some patients is due to an absent or
hypoplastic thymus. 22q11.2 deletion syndrome (22q11.2DS) may be first spotted when an
affected newborn has heart defects or convulsions from hypocalcemia due to malfunctioning
parathyroid glands and low levels of parathyroid hormone (parathormone).
Affected individuals may also have other kinds of birth defects including kidney abnormalities and
significant feeding difficulties as babies. Gastrointestinal issues are also very common in this
patient population. Digestive motility issues may result in constipation.
Disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet
levels), and psychiatric illnesses are common late-occurring features.
Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk
of schizophrenia. Studies provide various rates of 22q11.2DS in schizophrenia, ranging from 0.5 to
2.0% and averaging about 1.0%, compared with the overall estimated 0.025% risk of the
22q11.2DS in the general population.
Salient features can be summarized using the mnemonic CATCH-22 to describe 22q11.2DS, with
the 22 signifying the chromosomal abnormality is found on the 22nd chromosome, as below:
• Cardiac abnormality (commonly interrupted aortic arch, truncus arteriosus and tetralogy of
Fallot)
• Abnormal facies
• Thymic aplasia
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• Cleft palate
• Hypocalcemia/hypoparathyroidism
Some experts support changing the name of both DiGeorge and velocardiofacial syndromes to
CATCH-22. The International 22q11.2 Foundation, through its Same Name Campaign, advocates
for the consistent use of 22q11.2 deletion syndrome.
Individuals with a 22q11.2 deletion can have many possible features, ranging in number of
associated features and from the mild to the very serious.
Symptoms shown to be common include:
• Congenital heart disease (40% of individuals), particularly conotruncal malformations
(interrupted aortic arch (50%), persistent truncus arteriosus (34%), tetralogy of Fallot, and
ventricular septal defect)
• Cyanosis (bluish skin due to poor circulation of oxygen-rich blood)
• Palatal abnormalities (50%), particularly velopharyngeal incompetence, submucosal cleft
palate, and cleft palate; characteristic facial features (present in the majority of Caucasian
individuals) including hypertelorism
• Learning difficulties (90%), including cognitive deficits, attention deficit disorders [18]
• Hypocalcemia (50%) (due to hypoparathyroidism)
• Significant feeding problems (30%)
• Renal anomalies (37%)
• Hearing loss (both conductive and sensorineural) (hearing loss with craniofacial
syndromes)
• Laryngotracheoesophageal anomalies
• Growth hormone deficiency
• Autoimmune disorders
• Immune disorders due to reduced T cell numbers
• Seizures (with or without hypocalcemia)
• Skeletal abnormalities
• Psychiatric disorders
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This syndrome is characterized by incomplete penetrance. Therefore, there is a marked variability
in clinical expression between the different patients. This often makes early diagnosis difficult.
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Triple X Syndrome:
Description: Triple X Syndrome is characterized by an extra X chromosome in each of a female’s
cells. It does not cause any unusual physical features but is associated with the increased risk of
learning disabilities and delayed development of speech and language skills.
➡️ Signs and symptoms:
Because the vast majority of triple X females are never diagnosed, it may be very difficult to make
generalizations about the effects of this syndrome. The samples that were studied were small and
may be nonrepresentative. Because of the lionization, inactivation, and formation of Barr bodies in
all female cells, only one X chromosome is active at any time. Thus, triple X syndrome most often
has only mild effects or has no effects. The symptoms vary from person to person, with some
women being more affected than others.
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Williams Syndrome:
Description: Williams’s syndrome is caused by a deletion of genetic material from portions of the
long arm of chromosome 7, a region that consists of more than 25 genes. Researchers have
identified a few of the specific genes related to Williams syndrome, but the relationship between
most of the genes in the deleted region and the symptoms of Williams syndrome is still unknown.
➡️ Signs and symptoms:
The most common symptoms of Williams’s syndrome are heart defects and unusual facial
features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive)
and low muscle tone. Individuals with Williams’s syndrome tend to have widely spaced teeth, a
long philtrum, and a flattened nasal bridge.
Most individuals with Williams’s syndrome are highly verbal relative to their IQ, and are overly
sociable, having what has been described as a "cocktail party" type personality. Individuals with
WS hyperfocus on the eyes of others in social engagements.
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Cri Du Chat Syndrome:
Description: Cri du Chat syndrome results from missing a piece of chromosome 5. Symptoms
include a high-pitched cry that sounds like a cat, downward slant of the eyes, partial webbing or
fusing of fingers or toes, and slow or incomplete development of motor skills.
➡️ Signs and symptoms:
The syndrome gets its name from the characteristic cry of affected infants, which is similar to that
of a meowing kitten, due to problems with the larynx and nervous system. About 1/3 of children
lose the cry by age of 2 years. Other symptoms of cri du chat syndrome may include:
• feeding problems because of difficulty in swallowing and sucking;
• low birth weight and poor growth;
• severe cognitive, speech, and motor delays;
• behavioral problems such as hyperactivity, aggression, outbursts, and repetitive
movements;
• unusual facial features which may change over time;
• excessive drooling;
• small head and jaw;
• wide eyes;
• skin tags in front of eyes.
Other common findings include hypotonia, microcephaly, growth retardation, a round face with full
cheeks, hypertelorism, epicanthal folds, down-slanting palpebral fissures, strabismus, flat nasal
bridge, down-turned mouth, micrognathia, low-set ears, short fingers, single palmar creases, and
cardiac defects (e.g., ventricular septal defect[VSD], atrial septal defect [ASD], patent ductus
arteriosus [PDA], tetralogy of Fallot). Infertility is not associated with Cri du chat.
It has also been observed that people with the condition have difficulties communicating. While
levels of proficiency can range from a few words to short sentences, it is often recommended by
medical professionals for the child to undergo some sort of speech therapy/aid with the help of a
professional.
Less frequently encountered findings include cleft lip and palate, preauricular tags and fistulas,
thymic dysplasia, intestinal malrotation, megacolon, inguinal hernia, dislocated hips,
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cryptorchidism, hypospadias, rare renal malformations (e.g., horseshoe kidneys, renal ectopia or
agenesis, hydronephrosis), clinodactyly of the fifth fingers, talipes equinovarus, pes planus,
syndactyly of the second and third fingers and toes, polysyndactyly, and hyperextensible joints.
The syndrome may also include various dermatoglyphics, including transverse flexion creases,
distal axial triradius, increased whorls and arches on digits, and a single palmar crease.
Late childhood and adolescence findings include significant intellectual disability, microcephaly,
coarsening of facial features, prominent supraorbital ridges, deep-set eyes, hypoplastic nasal
bridge, severe malocclusion, and scoliosis. Affected females reach puberty, develop secondary
sex characteristics, and menstruate at the usual time. The genital tract is usually normal in
females except for a report of a bicornuate uterus. In males, testes are often small, but
spermatogenesis is thought to be normal.
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Trisomy 13:
Description: Trisomy 13, also called Patau syndrome, is a disorder in which an individual has three
copies of genetic material from chromosome 13, rather than two. It can occur in three forms:
Trisomy 13, which has a third chromosome 13 in all cells; Trisomy 13 mosaicism, which has a third
chromosome 13 in some cells; and partial Trisomy, which has the presence of part of an extra
chromosome 13 in the cells.
➡️ Signs and symptoms:
Of those fetuses that do survive to gestation and subsequent birth, common abnormalities may
include:
• Nervous system
• Intellectual disability and motor disorder
• Microcephaly
• Holoprosencephaly (failure of the forebrain to divide properly).
• Structural eye defects, including microphthalmia, Peters' anomaly, cataract, iris or fundus
(coloboma), retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss,
and optic nerve hypoplasia
• Meningomyelocele (a spinal defect)
• Musculoskeletal and cutaneous
• Polydactyly (extra digits)
• Cyclopia
• Proboscis
• Congenital trigger digits
• Low-set ears
• Prominent heel
• Deformed feet known as rocker-bottom feet
• Omphalocele (abdominal defect)
• Abnormal palm pattern
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• Overlapping of fingers over thumb
• Cutis aplasia (missing portion of the skin/hair)
• Urogenital
• Abnormal genitalia
• Kidney defects
• Other
• Heart defects (ventricular septal defect) (Patent Ductus Arteriosus)
• Dextrocardia
• Single umbilical artery
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Cat Eye Syndrome:
Description: For individuals with cat eye syndrome, the short arm (known as 22p) and a small
region of the long arm (22q) of chromosome 22 are present three or four times, rather than twice.
Characteristic features of the disorder include mild growth delays before birth, mild mental
deficiency, and malformations of the skill and facial region, the heart, the kidneys, and/or the anal
region.
➡️ Signs and symptoms:
• Unilateral or bilateral iris coloboma (absence of tissue from the colored part of the eyes)
• Downward-slanting Palpebral fissures (openings between the upper and lower eyelids)
• Preauricular pits/tags (small depressions/growths of skin on the outer ears)
• Cardiac defects (such as TAPVR)
• Kidney problems (missing, extra, or underdeveloped kidneys)
• Short stature
• Scoliosis/Skeletal problems
• Intellectual disability – although most are intellectually normal, CES patients occasionally
exhibit moderate to severe disability.
• Micrognathia (smaller jaw)
• Hernias
• Cleft palate
• Rarer malformations can affect almost any organ
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⑦ CONCLUSION:
Chromosomal disorders are a diverse group of genetic conditions caused by abnormalities in the
structure or number of chromosomes. Throughout this investigatory project, we have explored
various aspects of chromosomal disorders, including their causes, types, symptoms, and impact
on individuals.
1. Causes of Chromosomal Disorders: Chromosomal disorders can arise from different causes,
such as errors during cell division (e.g., nondisjunction), chromosomal rearrangements (e.g.,
translocations), or mutations in specific genes responsible for chromosomal stability.
2. Types of Chromosomal Disorders: There are numerous types of chromosomal disorders,
including Down syndrome (trisomy 21), Turner syndrome (monosomy X), Klinefelter syndrome
(XXY), and many others. Each disorder is characterized by specific chromosomal abnormalities
and presents with distinct symptoms.
3. Symptoms and Impact: Chromosomal disorders can manifest in a wide range of symptoms and
can affect various aspects of an individual's health and development. These may include physical
characteristics (such as facial features or body abnormalities), cognitive impairments,
developmental delays, reproductive issues, and an increased risk of certain medical conditions.
In conclusion, chromosomal disorders are complex genetic conditions that have a profound impact
on affected individuals and their families. Understanding the causes, types, symptoms, and
available support systems is crucial for early detection, intervention, and providing appropriate
care. Continued research and advancements in genetic technology offer hope for further
understanding and potentially developing new treatments or preventive measures for
chromosomal disorders in the future.
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⑧ BIBLIOGRAPHY:
⦿ WIKIPEDIA.ORG
⦿ GOOGLE.COM
⦿ YOURGENOME.ORG
⦿ BING.COM
⦿ GOOGLE IMAGES
⦿ YOUTUBE.COM
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