Genetic Disorder — NCERT Solutions

Given: A set of fundamental genetic terms to be defined.

Definitions:

(i) Dominant:
A dominant allele is one that expresses its effect (trait) in the phenotype even when only one copy is present (i.e., in heterozygous condition). It masks the effect of the recessive allele. It is conventionally represented by a capital letter (e.g., $A$).

(ii) Recessive:
A recessive allele is one whose effect is masked by the dominant allele when both are present together. It expresses itself only when present in homozygous condition (i.e., two copies of the recessive allele are present). It is represented by a lowercase letter (e.g., $a$).

(iii) Homozygous:
An organism is said to be homozygous for a particular gene locus when it carries two identical alleles at that locus on homologous chromosomes. It can be homozygous dominant ($AA$) or homozygous recessive ($aa$). Homozygous organisms breed true for that trait.

(iv) Heterozygous:
An organism is said to be heterozygous for a particular gene locus when it carries two different alleles at that locus on homologous chromosomes (e.g., $Aa$). The dominant allele is expressed in the phenotype, while the recessive allele remains hidden. Such organisms are also called carriers.

(v) Phenotype:
Phenotype refers to the observable physical, biochemical, or physiological characteristics of an organism that result from the interaction of its genotype with the environment. Examples include height, eye colour, blood group, and skin colour. Two organisms with different genotypes may have the same phenotype (e.g., $AA$ and $Aa$ both show the dominant phenotype).

(vi) Genotype:
Genotype refers to the complete genetic constitution (allelic composition) of an organism for a particular trait or for all traits. It represents the actual set of alleles present in the organism's genome. For example, for a gene with alleles $A$ and $a$, possible genotypes are $AA$, $Aa$, or $aa$. The genotype determines the potential phenotype of the organism.

Given: Down syndrome — a chromosomal disorder.

Origin (Cause):

• Down syndrome is caused by trisomy of chromosome 21, meaning the affected individual has three copies of chromosome 21 instead of the normal two, giving a total chromosome number of $2n = 47$.
• It arises due to non-disjunction during meiosis (usually meiosis I or II) in one of the parents, most commonly in the mother during oogenesis.
• Non-disjunction means the failure of homologous chromosomes (or sister chromatids) to separate properly during cell division.
• The risk of Down syndrome increases significantly with advanced maternal age (above 35 years).
• In rare cases (~4%), it can result from Robertsonian translocation, where chromosome 21 attaches to another chromosome (usually chromosome 14).
• Karyotype notation: $47, +21$ (or $47, XX, +21$ in females; $47, XY, +21$ in males).

Symptoms:

1. Physical features: Short stature, round and flat face, small nose, upward-slanting eyes with epicanthal folds (Mongoloid appearance).
2. Hands: Short, broad hands with a single palmar crease (simian crease), short fingers.
3. Intellectual disability: Mild to moderate mental retardation; IQ typically ranges from 25–75.
4. Delayed development: Delayed motor milestones (sitting, walking) and speech development.
5. Congenital heart defects: Present in approximately 40–50% of cases.
6. Hypotonia: Poor muscle tone (floppiness) at birth.
7. Increased susceptibility to respiratory infections, leukaemia, and Alzheimer's disease in later life.
8. Infertility: Males are usually infertile; females may occasionally be fertile.
9. Protruding tongue and open mouth appearance.

Treatment:

• There is no cure for Down syndrome as it is a chromosomal condition.
• Management is symptomatic and supportive:

1. Early intervention programmes: Speech therapy, physiotherapy, and occupational therapy to improve motor and communication skills.
2. Special education: Tailored educational programmes to maximise intellectual potential.
3. Surgical correction of congenital heart defects if present.
4. Regular medical monitoring for associated conditions (thyroid disorders, hearing/vision problems, infections).
5. Psychological and social support for the individual and family.

• Prenatal diagnosis (amniocentesis, chorionic villus sampling, or triple/quadruple marker test) can detect the condition before birth.

Conclusion: Down syndrome is the most common autosomal chromosomal disorder, caused by trisomy 21, and is managed through multidisciplinary supportive care.

Given: Klinefelter syndrome — a sex chromosomal disorder.

Origin (Cause):

• Klinefelter syndrome occurs in males and is caused by the presence of one or more extra X chromosomes.
• The most common karyotype is $47, XXY$ (total 47 chromosomes), though variants like $48, XXXY$ or $48, XXYY$ also exist.
• It arises due to non-disjunction of sex chromosomes during meiosis in either parent:
• If non-disjunction occurs in the mother during meiosis I or II, an egg with two X chromosomes ($XX$) is formed; when fertilised by a normal $Y$-bearing sperm, the result is $XXY$.
• If non-disjunction occurs in the father during meiosis I, a sperm with both $X$ and $Y$ ($XY$) is formed; when fertilised with a normal $X$-bearing egg, the result is $XXY$.
• Frequency: Approximately 1 in 500–1000 live male births.

Symptoms:

1. Hypogonadism: Small, firm testes (testicular atrophy) and reduced testosterone production.
2. Infertility: Azoospermia (absence of sperm) — the most consistent feature; affected males are almost always infertile.
3. Gynaecomastia: Abnormal development of breast tissue in males.
4. Tall stature with long legs and a relatively short trunk.
5. Sparse body and facial hair due to androgen deficiency.
6. Mild intellectual disability or learning difficulties (especially in language and reading) in some individuals.
7. Feminine body contour with broad hips.
8. Delayed or incomplete puberty.
9. Increased risk of osteoporosis, type 2 diabetes, and autoimmune disorders.

Treatment:

• There is no cure as it is a chromosomal condition.
• Management is hormonal and supportive:

1. Testosterone replacement therapy (TRT): Started at puberty; helps develop secondary sexual characteristics (facial hair, muscle mass, deepening of voice), improves mood, energy, and bone density.
2. Treatment of gynaecomastia: Surgical removal (mastectomy) if required.
3. Fertility treatment: Assisted reproductive techniques such as Testicular Sperm Extraction (TESE) combined with Intracytoplasmic Sperm Injection (ICSI) may help some men father children.
4. Speech therapy and educational support for learning difficulties.
5. Psychological counselling for the patient and family.
6. Regular monitoring for associated conditions (metabolic syndrome, osteoporosis).

Conclusion: Klinefelter syndrome ($47, XXY$) is the most common sex chromosomal disorder in males, caused by non-disjunction, and is primarily managed with testosterone replacement therapy.