Patho module 1 genetic disorders

Autosomal Recessive Disorders

Genetic conditions caused by mutations on a single gene that are passed from parents to offspring regardless of biological sex.

1. Inheritance Pattern

   • The disease only manifests if the fetus inherits mutated gene copies from both parents (homozygous).

   • If an individual inherits only one mutated copy (heterozygous), they are a carrier but do not express the disease.

Tay-Sachs Disease

An autosomal recessive lysosomal storage disorder characterized by a complete absence of the enzyme hexosaminidase A.

1. Pathophysiology: Causes a toxic buildup of lipids (fats) in nerve cells.

2. Symptoms: Includes an exaggerated startle (moro) reflex between 5 and 10 months of age.

3. Demographics: Most prevalent in populations of Jewish/Mediterranean descent.

4. Prognosis: Early onset in life; death usually occurs by the age of 5.

Phenylketonuria (PKU)

An autosomal recessive metabolic disorder resulting from a deficiency in the enzyme phenylalanine hydroxylase.

1. Effect: The lack of enzyme leads to toxic accumulation of phenylalanine, causing central nervous system damage.

2. Progression: Infants appear normal at birth but fail to meet developmental milestones (sitting, rolling, walking).

3. Screening: Diagnosed via a heel stick blood test on day 3 of life.

4. Management: Requires a lifelong diet low in protein and limited in starches.

Cystic Fibrosis (CF)

An autosomal recessive mutation on the 7^{th} pair of chromosomes that disrupts chloride channels in the body.

1. Clinical Manifestations: Results in the production of thick, sticky mucus in the lungs and pancreas.

2. Diagnosis: Identified by a sweat chloride test due to the child's salty skin (caused by errors in chloride movement in/out of cells).

3. Systems Affected: Primarily the respiratory and digestive systems.

Autosomal Dominant Disorders

Genetic conditions where a single gene mutation from one affected parent is sufficient to pass the trait to offspring, regardless of sex.

• The condition can be expressed in both homozygous and heterozygous states.

Neurofibromatosis

An autosomal dominant disorder characterized by the growth of tumors from Schwann cells (nerve support cells).

1. Type 1:

   • Presence of scoliosis.

   • "Café au lait" spots (light brown patches on the skin).

2. Type 2:

   • Tumors located on the acoustic nerve of the ear.

   • Often results in hearing loss; treatment involves tumor removal.

Marfan Syndrome

An autosomal dominant connective tissue disorder with a later onset in life.

1. Physical Features: Tall stature, exceptionally long extremities, thin narrow face, and a small lower jaw.

2. Complications: Risk of lens displacement in the eyes and life-threatening aortic aneurysms or valve defects (e.g., coarctation of the aorta).

3. Historical Example: Abraham Lincoln is a famous figure believed to have had this syndrome.

Multifactorial Disorders: Cleft Lip and Cleft Palate

Congenital conditions where the upper lip or the roof of the mouth (palate) fails to fuse during development.

1. Presentation: Obvious at birth; leads to feeding and speech difficulties.

2. Risk Factors: Increased incidence if the mother smokes or has diabetes during pregnancy.

Fetal Alcohol Syndrome (FAS)

A multifactorial condition caused by maternal alcohol consumption during pregnancy.

1. Pathophysiology: The amniotic fluid acts as a reservoir for alcohol, extending the fetus's exposure time.

2. Physical Indicators: Thin upper lip, smooth philtrum (the groove above the lip), and short palpebral fissures (eye length).

3. Cognitive Effects: Significant cognitive and developmental impairment.

Fragile X Syndrome

A sex-linked disorder characterized by a failure to produce the protein necessary for neural tube development.

1. Physical Features: Prominent jaw and forehead, large ears, long narrow face, and macroorchidism (large testes).

2. Symptoms: Speech and language delays, seizures, and common placement on the autism spectrum.

3. Inheritance: If the father is affected, all daughters will be carriers.

Down Syndrome (Trisomy 21)

A chromosomal disorder involving an extra (3^{rd}) copy of the 21^{st} chromosome.

1. Physical Traits: Small square head, upward-slanting eyes, small low-set ears, protruding tongue, and a single palmar (Simian) crease.

2. Risks: Increased risk associated with advanced maternal age; patients have higher rates of leukemia, congenital heart defects, and Alzheimer’s disease.

Turner’s Syndrome (Monosomy X)

A chromosomal disorder (45, X) where a female is born with only one X chromosome.

1. Characteristics: Short stature, increased weight, webbed neck, drooping eyelids, and a small lower jaw.

2. Infertility: Ovaries are replaced by non-functional gonadal streaks.

3. Treatment: Managed with estrogen and growth hormone replacement therapy.

Klinefelter’s Syndrome (Polysomy X)

A chromosomal disorder occurring in males with an XXY genetic makeup.

1. Physical Traits: Tall stature with long legs, short obese trunk, small penis and testes, and gynecomastia (breast tissue development).

2. Health Risks: Increased risk for breast cancer, impotence, and behavioral issues.