Genetic Disorders Explained

Genetic Disorders

• Genetic diseases occur when a person has one or more abnormal, missing, extra, inactivated, or overly active genes, leading to a medical condition.

Understanding Genetic Disorders

• Genes serve as the building blocks of heredity and are passed from parent to child.
• Genes reside within cells of all organisms, present in a large molecule called deoxyribonucleic acid (DNA).
• DNA holds instructions for making proteins.
• DNA comprises different combinations of four nucleic acids: adenine, thymine, cytosine, and guanine, arranged in varying lengths.
• Proteins perform most of the work within cells.
• Proteins transport molecules, build structures, break down toxins, and perform maintenance tasks.
• Human cells typically contain 23 pairs of chromosomes.
• In each pair of chromosomes, one comes from the father and the other from the mother.
• Mutation, or change, can occur in a gene or genes.
• Mutation alters a gene's instructions for making a protein, which causes the protein to malfunction or become entirely absent.
• A medical condition may arise due to this.
• A person can inherit a gene mutation from one or both parents.

Heredity of Genetic Disorders

• A person's DNA exists within two sets of chromosomes, with each parent contributing one set of 23 chromosomes, totaling 23 pairs of chromosomes.
• X and Y chromosomes, known as sex chromosomes, differentiate males from females.
• Females possess a pair of X chromosomes, while males possess one X and one Y chromosome.
• Genetic conditions can arise from mutations in sex chromosomes, affecting males and females differently.
• Individuals with only one copy of a mutated gene typically do not experience disease symptoms but are termed "carriers," capable of passing the trait to their offspring.
• Genetic conditions are commonly inherited, transmitted from parents to children.
• Some genetic disorders stem from mutations occurring during the development of the egg, sperm, or embryo, even without a family history of the disorder.

Gene Mutation and Types

• A gene mutation signifies a permanent alteration in the DNA sequence constituting a gene.
• Types of gene mutations:
  • Acquired mutations: Occur during a person's lifetime and are present only in specific cells, not throughout the body.
  • Hereditary mutations: Inherited from a parent and are present throughout a person's life in virtually every cell in the body.

Hereditary Mutation

• Hereditary mutations are inherited from a parent and are in virtually every cell
• Also known as Germ line mutations they are in the parents egg and sperm cells
• The fertilized cell after union of the sperm and egg receive DNA from both parents
• If the DNA has a mutation, the growing child will have the mutation in each of their cells

Acquired Mutation

• Acquired mutations occur sometime during a persons life
• They are only present in certain cells
• Environmental factors like UV radiation can cause them
• They can also occur if a mistake is made during DNA copying in cell division
• Acquired mutations in Somatic cells (not sperm & egg) cannot be passed on to the next generation.

Types of Genetic Disorders

• Single-gene disorders: Mutation affects one gene; Sickle cell anemia is an example.
• Chromosomal disorders: Chromosomes (or parts of chromosomes) are missing or changed.
  • Chromosomes hold our genes.
  • Down syndrome is a chromosomal disorder.
• Complex disorders: Mutations in two or more genes.
  • Lifestyle and environment play a role; Colon cancer is an example.

Diagnosing Genetic Disorders

• Genetic tests involve blood and tissue analysis to detect genetic disorders.
• Purposes of these tests
  • Finding genetic diseases in unborn babies
  • Determining if individuals carry a disease gene that can be passed to children
  • Screening embryos for disease
  • Testing adults for genetic diseases before symptoms manifest
  • Diagnosing individuals with disease symptoms
  • Determining the optimal medicine type and dosage for a patient

Physical Examination

• Distinctive facial features sometimes indicate a diagnosis of a genetic disorder.
• Geneticists conduct thorough physical examinations, measuring head circumference, distance between eyes, and length of arms and legs.
• Specialized examinations, such as neurological or ophthalmologic exams, may be performed.
• Imaging studies (X-rays, CT scans, MRI) visualize internal body structures.

Personal Medical History

• An individual's health information, traced back to birth, gives indications on a genetic diagnosis.
• Medical history encompasses past health problems, hospitalizations, surgeries, allergies, medications, and prior medical or genetic testing results.

Family Medical History

• Genetic conditions often run in families, making family health information a critical diagnostic tool.
• Doctors or genetic counselors inquire about health conditions in parents, siblings, children, and extended relatives.
• This gives information about the diagnosis and inheritance pattern of genetic conditions.

Labratory Tests

• Genetic testing can be molecular, chromosomal, and biochemical - allowing the diagnosis of disorders.
• Other lab tests can assess the levels of certain substances in blood and urine, suggesting diagnosis.

Prenatal Diagnosis

• Prenatal diagnosis can detect fetal abnormalities via ultrasound or testing for characteristic substances through invasive procedures like amniocentesis, which involves inserting probes or needles into the uterus.

Huntington's Disease (HD)

• HD involves degeneration of nerve cells in brain and central nervous system.
• It is an autosomal dominant hereditary condition, with a 50% chance of children developing and passing it on if a parent has it.
• Treatment aims to limit the course of the disease, typically showing itself between ages 30-40, with rare forms beginning in childhood.
• Symptoms include uncontrolled movement (chorea), difficulty swallowing, behavioral changes, balance difficulty, and memory, speech, and cognitive loss.

Down Syndrome

• Characterized as a common chromosomal abnormality where an extra copy of genes occur on chromosome 21.
• Occurs in approximately 1 in 1000 newborns, particularly in older expectant mothers.
• Although pre-natal testing can detect it, the babies affected typically show symptoms at birth.
  • Decreased muscle tone in the face, developmental delays, and heart and digestive system defects

Down Syndrome - Etiology

• Trisomy 21: The child possesses three copies of chromosome 21 in all cells due to abnormal cell division during sperm or egg cell development.
• Mosaic Down Syndrome: Children have a mix of normal and abnormal cells (extra copy of chromosome 21) because of abnormal cell division after fertilization.
• Translocation Down Syndrome: Part of chromosome 21 attaches (translocates) onto another chromosome before or at conception. These children have the usual two copies of chromosome 21 plus additional material from the translocated chromosome.

Duchenne Muscular Dystrophy

• Symptoms of Duchenne Muscular Dystrophy show before age six.
• The condition causes fatigue, muscle weakness (starts in legs), progresses to the upper body causing wheelchair use by age 12.
• Mostly affects boys
• Symptoms are heart and respiratory difficulties, chest/deformity and mental retardation.

Treatment

• Most treatment options address symptoms to improve patient quality of life.
• Gene therapy introduces a healthy gene to a patient and alleviates defects caused by a faulty gene.
• Gene therapy has issues delivering genes to the appropriate organ or tissue.

Prognosis

• Not all genetic disorders are fatal
• No known cures for genetic diorders exist
• Genetic disorders like Down syndrome affect stages of development.
• Other genetic diorders like muscular dystrophy result in purely physical symptoms
• Some disorders, such as Huntington's Disease, show no signs until adulthood