Genetic Diseases

Not necessarily hereditary but increased incidence among family members

Familial

What type of mutations can be transmitable Somatic or Germ cell

Germ cell mutations (somatic cannot)

Examples of larger, chromosome level Cytogenetic changes

• Amplification

• Deletion

• Translocation

• Inversion

Changes in regulation of gene expression, not sequence. Often caused by the environment

Epigenetic Changes

Only one mutated copy of gene is needed for disease

Autosomal Dominant

Two mutated copies required

Autosomal recessive

What type of mutation is Marfan Syndrome

Autosomal Dominant - single gene

Etiology of Marfan

Mutation in Fibrillin-1 gene FBN1

What does FBN-1 Gene do

ECM component of Elastic fibers

What has this clinical Presentation: Long arms, legs, fingers / toes, flexible joints, high arched palate, ocular dislocation, mitral prolapse, aortic aneurism and dissection

Marfan syndrome

Familial Hypocholesterolemia is what type of mutation

Autosomal Dominant single gene

Etiology of Familial Hypercholesterolemia

Mutation in LDL receptor gene (loss of function, no LDL uptake so stays in plasma)

What type of mutation is Cystic Fibrosis

Autosomal Recessive (MOST COMMON)

Etiology of Cystic Fibrosis

Mutation in CFTR Gene, Effects Chloride ion transport leads to thick mucus and salty sweat

Clincial presentaiton:

• Chronic respiratory infection

• Pancreatic insufficiency

• Salty sweat

• Poor growth

Cystic fibrosis

What mutation is Lysosomal Storage disease

Autosomal recessive

What happens in Lysosomal storage disease?

Deficiency of lysosome enzymes, cannot degrade material ingested and builds up in lyosomes.

Group who more commonly has Lysosomal storage diseases

Ashkenazi Jews

Clinical Presentation:

• Fatal in childhood

• Progressive

• CNS involvement

• Organ enlargement

• Gaucher: radioluc. jaw lesions

• Macroglossia and Impacted teeth

Lysosomal Storage disease

What mutation causes cleft palate

Complex multi genetic disorder

Etiology for Cleft palate

• Assoc. with 400 developmental syndromes

  • Single gene

  • Chromosome anomalies

• Non-syndromic:

  • Major and minor genes

  • Environmental factors

    • Maternal alcohol and cigarettes

Different clinical presentations of Cleft palate

• Full Cleft palate between oral and nasal cavity

• Sub-mucous palatal cleft

• Bifid uvula

Is addition or loss of a chromosome more severe?

Loss - usually not compatible with life.

Imbalance of autosomal or sex hormones tolerated better

Sex hormones

Are cytogenetic disorders inherited from parents

No, and recurrence in siblings is low

3 Copies (trisomy) of chromosome 21

Down syndrome

Clinical Presentation:

• Intellectual disability

• Distinct facial features

• Increased leukemia risk

• Hypotonia

• Short stature

• Inc. risk congen. heart dis.

Trisomy 21: down syndrome

Clinical presentation:

• Macroglossia

• Gingivitis

• Candidiasis

• Resistance to caries

• Bruxism

• Mouth breathing

• Narrow palate

• delayed tooth eruption

Trisomy 21: Down syndrome

3 copies of Chromosome 18

Edwards Syndrome

Clinical Presentation:

• Heart and lung defects

• Prominent back of head

• Malformed and low ears

• Micrognathia

• Index finger overlap

• clubbed feet

• Short median survival 2.5-14 days

Trisomy 18 Edwards syndrome

Trisomy 13

Patau syndrome

Clinical Presentation:

• Intellectual disability

• Microcephaly

• Micropthalmia (small eyes)

• Cleft lip / palate

• Polydactyly

• Cardiac / renal defects

• Club feet

Trisomy 13 Patau syndrome

Two X chromosomes and one Y chromosome. 47, XXY karyotype

Klinefelter Syndrome

Clinical presentation:

• Tall stature

• Reduced facial and body hair

• Gynecomastia

• Testicular atrophy

• Varicose veins

• Mild intellectual impairment

• OFTEN DIAGNOSED AFTER PUBERTY

Klinefelter syndrome

Female, 45 X karyotype. Missing X chromosome

Turner Syndrome

Clinical Presentation:

• Short stature

• Webbed neck

• Low posterior hairline

• Amenorrhea (lack of period)

• Decreased secondary female sex characteristics

• Cardiovasc. abnormalities

• Hypothyroidism

Turner Syndrome (45 X karyotype)