Genetic Disorders Overview

Genetic Disorders

• Cri-du-chat Syndrome: Characterized by a "cry" like cat due to larynx development issues. Features include a small cranium, small jaw, and a moon-shaped face. Incidence: 1/100,000.

• Down Syndrome (Trisomy 21): Increased risk with maternal age. Features include short stature, broad hands, upward-slanting eyes, stubby fingers/toes, a large tongue, and small ears. Associated with respiratory/heart disease, leukemia. Incidence: 1/750 (early 20s), 1/1500 (general), 1/25 (>40).

• Edwards Syndrome (Trisomy 18): Cleft lip/palate, elongated skull, narrow pelvis, rocker-bottom feet, and malformed heart. High mortality rate - death within the first year. Incidence: 1/5000.

• Jacob's Syndrome (47, XYY): Caused by nondisjunction of the Y chromosome. Features include tall stature, acne, and low mental ability. Incidence: 1/1000.

• Klinefelter Syndrome (47, XXY): Extra X chromosome. Features include tall stature, small testicles, breast enlargement, and sterility. Affects males only. Incidence: 1/1000.

• Patau Syndrome (Trisomy 13): Severe cerebral malformations, pronounced cleft lip/palate, broad nose, polydactyly (extra fingers/toes), small cranium, and non-functional eyes. High mortality rate—death within the first year. Incidence: 1/15,000.

Triple X Syndrome

• Females only.
• No specific abnormalities.
• Often mentally normal.
• Taller.
• Underdeveloped genitalia.
• Limited fertility.
• Possible neuromotor delays.
• Incidence: 1/1000.

Turner Syndrome

• An X-chromosome related disorder, usually in females.
• X-carrying sperm fertilizes an egg lacking an X.
• Affects only females.
• Short stature.
• Missing X chromosome
• Webbed neck
• Broad shoulders
• Underdeveloped breasts
• Infertile.
• No menstruation.
• Incidence: 1/2500.

Mosaicism

• An individual with two or more genetically different cell populations.
• Due to nondisjunction in mitosis, not meiosis.
• May be in egg, sperm or blood cells.

Chimerism

• A person has two or more genetically different cell populations from more than one zygote.
• Due to fusion of zygotes after fertilization or twin-twin cell exchange.

Structural Anomalies in Chromosomes

• Reciprocal Translocation: Terminal segments from two different chromosomes are exchanged. No gain or loss of genetic material just rearranged.

• Inversion: A chromosome segment breaks off and reattaches in the reverse orientation. No gain or loss of genetic material.

• Ring Formation: A chromosome breaks off and the ends fuse, forming a ring shape.

• Terminal Deletion: The end segment of a chromosome is lost.

• Interstitial Deletion: The middle segment of a chromosome is lost.

• Isochromosome: A chromosome with identical arms (one long, one short).

Autosomal Disorders

• Down Syndrome (Trisomy 21): Extra copy of chromosome 21. Prenatal testing is available. Risk increases with maternal age. Features include mental retardation, upward-slanting eyes, small mouth, and abnormal ear shape.

• Patau Syndrome (Trisomy 13): Extra copy of chromosome 13. High mortality rate. Features include severe cerebral malformations, cleft lip/palate, broad nose, polydactyly, small cranium, non-functional eyes.

• Edwards Syndrome (Trisomy 18): Extra copy of chromosome 18. Very severe. Most infants die within first few weeks.

Deletion Disorders

• Angelman Syndrome: Characterized by inappropriate laughter, poor coordination, and mental retardation.

• Prader-Willi Syndrome: Features include obesity, mild mental retardation, and extreme hunger.

Sex Chromosome Disorders

• Klinefelter Syndrome (47, XXY): Extra X chromosome in males. Symptoms include tall stature, small testicles, breast enlargement, sterility, and mild learning difficulties.

• Turner Syndrome (45, X): Missing or incomplete X chromosome in females. Marked by short stature, ovarian failure, normal intelligence, underdeveloped breasts.

Single Gene Disorders

• Cystic Fibrosis: Genetic disorder affecting the lungs and pancreas, producing thick mucus. Common in Caucasians.

• Hemophilia: Sex-linked disorder affecting blood clotting, which is rare in females.

• Sickle Cell Anemia: Blood disorder characterized by abnormal hemoglobin, resulting in sickle-shaped red blood cells. Screening is useful in populations where malaria is present.

• Phenylketonuria (PKU): Genetic disorder affecting the breakdown of phenylalanine, requiring a special diet.

Chromosomal Mutations

• Deletion: Loss of one or more base pairs in DNA.
• Duplication: Copying of a chromosome segment and insertion into the same or another chromosome.
• Insertion: Addition of one or more base pairs to a DNA sequence.
• Inversion: Reversing the order of a DNA segment within a chromosome.
• Nondisjunction: Chromosomes fail to separate during cell division. May occur in meiosis or mitosis. Can lead to monosomy (missing chromosome) or trisomy (extra chromosome).
• Translocation: Transfer of a chromosome segment to another, non-homologous chromosome.
• Crossing Over: A natural process during meiosis (prophase I). Homologous chromosomes exchange genetic material.

Molecular Basis of DNA Sequence Variation

• Substitution: One base pair in the DNA sequence is replaced by another.

• Missense Mutation: Substitution of one amino acid for another.

• Nonsense Mutation: Substitution of one base pair shortens the sequence, thus interrupting the protein synthesis.

• Frameshift: Both deletions and insertions, can cause a frameshift if not a multiple of 3 (codon), affecting protein function.

• Null Mutation: Loss of a protein product from a gene, leading to a complete loss of function.

• Repetitive Elements: Repeated sequences of DNA.

• Identical Twins: Monozygotic; derive from a single fertilized egg that splits into two embryos.

• Fraternal Twins: Dizygotic; formed from two separate fertilized eggs.

Explore the key genetic disorders such as Cri-du-chat Syndrome, Down Syndrome, Edwards Syndrome, Jacob's Syndrome, and Klinefelter Syndrome. This quiz highlights their characteristics, incidence rates, and associated health issues. Test your knowledge on the impact and features of these genetic conditions.