BVII. Overview of Genetic Disorders Flashcards
i. Associated defects of Mendelian Disorders
- Marfan Syndrome
- Ehlers-Danlos Syndrome
ii. Associated with defects in receptor proteins
- Familial Hypercholesterolemia (FH)
iii. Associated with defects in enzymes
- Lysosomal Storage Diseases
- Tay-Sachs Disease
- Niemann-Pick Disease
- Gaucher’s Disease
- Mucopolysaccharidoses
- Glycogen Storage Diseases
- Alkaptonuria
iv. Associated with defects in proteins that regulate cell growth
- Neurofibromatosis
a) Multifactorial
b) Single Gene Disorders with non-classic inheritance - Triplet Repeat Mutation – Fragile X Syndrome
B. CYTOGENETIC DISORDERS
a) Involving autosomes
b) Involving sex chromosomes
c) Mutations in Mitochondrial genes
a) Involving autosomes
• Trisomy 21
• Trisomy 18
• Trisomy 13
• Cri-du-Chat
b) Involving sex chromosomes
• Klinefelter’s Syndrome
• XYY Syndrome
• Turner’s Syndrome
• Hermaphroditism
• Pseudohermaphroditism
c) Mutations in Mitochondrial genes
Leber’s Hereditary Optic Neuropathy
a) Genomic Imprinting ·
Prader-Willi Syndrome
Angelman’s Syndrome
is a disease caused in whole or in part by a change in the DNA sequence away from the normal sequence
genetic disorder
c) Mutations in Mitochondrial genes
mutation in one gene
monogenic disorder
mutations in multiple genes or by a combination of gene mutations and environmental factors
multifactorial inheritance disorder
by damage to chromosomes
changes in the number or structure of entire chromosomes, the structures that carry genes
● It is one of the most common inherited disorders of connective tissue.
Marfan Syndrome
● Autosomal dominant condition
Marfan Syndrome
● Cause: mutation in the FBN1 gene
Marfan Syndrome
mutations are associated with a broad continuum of physical features ranging from isolated features to a severe and rapidly progressive form in newborns.
○ FBN1
: abnormally longer than normal, dolichostenomelia, arachnodactyly, scoliosis, pectus excavatum, pectus carinatum, high palate, malocclusions
○ Bones
: angina pectoris, tachycardia, cystic medial degeneration, aortic dissection, heart murmur
○ Heart
: risk of spontaneous pneumothorax, emphysema, COPD, collapsed lung, sleep apnea
○ Lungs
: myopia or hyperopia, astigmatism, glaucoma, cataract, detachment or tear in the retina
○ Eyes
● Defect in the synthesis of collagen
Ehlers-Danlos Syndrome
: Hyper-flexible joints, Unstable joints that are prone to sprain, dislocation, subluxation and hyperextension, osteoarthritis, Chronic degenerative joint disease, Swan neck deformity of the fingers, Muscle fatigue that increases with use, hypotonia in infancy, Osteopenia, Stretchy ligaments and tendons, Tearing of tendons or muscles, Deformities of the spine, Myalgia and arthralgia
○ Musculoskeletal
: Stretchy skin with a velvety texture, Fragile skin, Easy bruising, Abnormal wound healing and scar formation, Redundant skin folds, Molluscoid pseudotumors, Subcutaneous spheroids, Fatty growths on forearms or shins, Angioplasia
○ Skin
: Fragile blood vessels, Life-threatening carotid-cavernous fistula, Unpredictable rupture of medium-sized arteries, Valvular heart disease
○ Cardiovascular
○ Orthostatic intolerance, Dilation and/or rupture of ascending aorta, Cystic medial necrosis, Varicose veins
: Raynaud’s phenomenon, Livedo reticularis
○ Vascular skin conditions
1 and 2
Autosomal dominant
COL5A1
COL5A2
COL1A1
Classical
3
Dominant/Recessive
Tenascin- X def.
COL3A1
TNX B
Hypermobility
4
Autosomal dominant
Type 3 collagen
COL3A1
Vascular
6
Autosomal recessive
Lysyl hydroxylase def.
PLOD1
Kyphoscoliosis
7A and 7B
Autosomal recessive
Type 1 collagen
COL1A1
COL1A2
Arthrochalasis
C
ADAMTS2
Dermatosparaxis
• An inherited condition that causes high levels of LDL cholesterol levels beginning at birth, and heart attacks at an early age.
Familial Hypercholesterolemia (FH)
• It is caused by a defect on chromosome 19
Familial Hypercholesterolemia (FH)
• The defect makes the body unable to remove low density lipoprotein from the blood.
Familial Hypercholesterolemia (FH)
• This results in a high level of LDL in the blood.
Familial Hypercholesterolemia (FH)
Familial Hypercholesterolemia (FH)
• Other names:
o Type II hyperlipoproteinemia;
o Hypercholesterolemic xanthomatosis;
o Low density lipoprotein receptor mutation
Familial Hypercholesterolemia (FH)
• Symptoms: Fatty skin deposits called (?) over parts of the hands, elbows, knees, ankles and around the cornea of the eye, Cholesterol deposits in the eyelids (?)
xanthomas
(xanthelasmas)
• A physical exam may show fatty skin growths called xanthomas and cholesterol deposits in the eye (?).
corneal arcus
• The disease is named for Warren Tay, a British ophthalmologist who in 1881 described a patient with a cherry-red spot on the retina of the eye.
Tay-Sachs Disease
• Life-threatening disease of the nervous system passed down through families.
Tay-Sachs Disease
occurs when the body lacks hexosaminidase A
Tay-Sachs Disease
caused by a defective gene on chromosome 15
Tay-Sachs Disease
• When both parents carry the defective TaySachs gene, a child has a 25% chance of developing the disease.
Tay-Sachs Disease
• The child must receive two copies of the defective gene, one from each parent, in order to become sick
Tay-Sachs Disease
• The disease is most common among the Ashkenazi
Tay-Sachs Disease
• Jewish population.
Tay-Sachs Disease
Tay-Sachs Disease
• Other names:
o GM2 gangliosidosis - Tay-Sachs;
o Lysosomal storage disease - TaySachs disease
Symptoms: Deafness, decreased eye contact, blindness, Decreased muscle tone (loss of muscle strength), loss of motor skills, paralysis, Slow growth and delayed mental and social skills, Dementia (loss of brain function), Increased startle reaction, Irritability, Seizures
Tay-Sachs Disease
• A primary deficiency of acid sphingomyelinase and the resultant accumulation of sphingomyelin.
Niemann-Pick Disease
• Affected cells and organs
Niemann-Pick Disease
Niemann-Pick Disease: Affected cells and organs
o phagocytic cells of spleen, liver, bone, marrow, lymph nodes, lungs
▪ stuffed with droplets or particles of the complex lipid, imparting a fine vacuolation or foaminess to the cytoplasm
o phagocytic cells of spleen, liver, bone, marrow, lymph nodes, lungs
o enlarged and vacuolated as a result of the storage of lipids.
o phagocytic cells of spleen, liver, bone, marrow, lymph nodes, lungs
- Classic infantile form, manifests itself in infancy with massive visceromegaly and severe neurologic deterioration
Niemann-Pick Disease Type A
- Visceral juvenile form, no neurologic disorders
Niemann-Pick Disease Type B
- Subacute/ Juvenile form, most common form of the disease, subtype with brain complications into C1 and C2
Niemann-Pick Disease Type C
(“Nova Scoatian type”)- caused by the mutation in the same gene as type C1, was originally separated from type C to delineate a group of patients sharing a common ancestry with otherwise identical disorders, no longer used.
Niemann-Pick Disease Type D
Niemann-Pick Disease Other names:
o lipid histiocytosis o neuronal cholesterol lipidosis
o neuronal lipidosis
o NPD
o sphingomyelin lipidosis
o sphingomyelin/cholesterol lipidosis
o sphingomyelinase deficiency
• rare genetic disorder that is one of a group called lysosomal storage disorders.
Gaucher’s Disease
• It is an inherited disorder that results in the accumulation of fatty molecules called cerebrosides in the body’s organs and tissues
Gaucher’s Disease
• It is caused by a missing or deficient enzyme called ‘glucocerebrosidase‘.
Gaucher’s Disease
• In people with Gaucher disease, the gene that would normally tell the body to produce this enzyme is altered
Gaucher’s Disease
• Signs and Symptoms: enlarged liver and spleen, low platelet and hemoglobin counts, problems with bones and joints
Gaucher’s Disease
• group of inherited lysosomal storage disorders
Mucopolysaccharidoses
Mucopolysaccharidoses
• In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (?) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes [?] to cells, tissues, and various organ systems of the body.
mucopolysaccharides or glycosaminoglycans
progressive damage
• Signs and Symptoms: “coarse” facial features, short stature, heart abnormalities, breathing irregularities, liver and spleen enlargement (hepatosplenomegaly), and/or neurological abnormalities
Mucopolysaccharidoses
• rare condition that changes the way the body uses and stores glycogen, a form of sugar or glucose.
Glycogen Storage Diseases
is passed down from parents to children (is hereditary). It is most often seen in babies or young children. But some forms may appear in adults.
Glycogen Storage Diseases
• Types of GSD
o Type I or von Gierke disease
o Type III, Cori disease, or Forbes disease
o Type IV or Andersen disease
This is the most common form of GSD. People with type I don’t have the enzyme needed to turn glycogen into glucose in the liver. Glycogen builds up in the liver. Symptoms often appear in babies around 3 to 4 months old. They may include low blood sugar (hypoglycemia) and a swollen belly because of an enlarged liver.
o Type I or von Gierke disease
People with this type don’t have enough of an enzyme called the debranching enzyme, which helps break down glycogen. The glycogen can’t fully break down. It collects in the liver and in muscle tissues. Symptoms include a swollen belly, delayed growth, and weak muscles.
o Type III, Cori disease, or Forbes disease
People with this type form abnormal glycogen. Experts think the abnormal glycogen triggers the body’s infection-fighting system (immune system). This creates scarring (cirrhosis) of the liver and other organs such as muscle and the heart.
o Type IV or Andersen disease
