Genetics Syndromes 1-15

Front 1

Down Syndrome (Trisomy 21)

Back 1

1. Dysmorphic features:

a. Upslanting palpebral fissures.

b. Epicanthal folds.

c. Short neck.

d. Single palmar crease.

e. Clinodactyly (incurved 5th finger).

2. Congenital heart disease (1/3)*.

3. Atlanto-axial instability*.

4. Duodenal atresia.

5. Hypotonia#.

6. Mental retardation#.

7. Hypothyroidism*.

8. Hearing loss*.

9. Vision concerns*.

10. Premature senility.

Front 2

Trisomy 13

Back 2

Typically lethal condition and most individuals die within the first year of life. Congenital malformations are common in ________ including central nervous system malformations and congenital heart disease. Specifically:

1. Growth retardation and microcephaly (small head).

2. Eye anomalies including microophthalmia and colobomas*.

3. Scalp defects.

4. Congenital cardiac malformations*.

5. Polydactyly.

6. Holoprosencephaly-type cerebral malformations*.

7. Severe Neurologic dysfunction.

8. Cleft lip and palate.

Front 3

Trisomy 18

Back 3

A. Genetics.

1. (47 +18).

2. Most are trisomy, 20% are translocations.

3. Advanced Maternal age is risk factor.


B. Phenotype:

________ is a typically lethal condition and most individuals die within the first year of life. Congenital malformations are common in _______ including central nervous system malformations and congenital heart disease. Specifically:
1. Failure to thrive/small for gestational age (low birth weight).

2. Congenital heart disease*.

3. Severe mental retardation*.

4. Dysmorphic features.

a. Characteristic hand clenching.

b. Rocker bottom feet.

Front 4

Turner Syndrome

Back 4

A. Genetics.

1. 45X.

2. Monosomy X. Common cause of miscarriage.

B. Phenotype:
1. Congenital Heart defects*.

2. Dysmorphic features.

a. Lymphedema.

b. Wide spaced nipples.

c. Webbed neck.
3. Renal malformations*.

4. Short stature (responds to growth hormone)*.

5. Failure to enter puberty * (provide estrogen treatment.

6. Infertility*.

7. Mild isolated learning disabilities*#.

Front 5

Klinefelter Syndrome

Back 5

A. Genetics.
1. Chromosomal 47XXY.

2. 1/1000 male births.


B. Clinical Phenotype:

1. (Tall and thin).

2. Hypogonadism at puberty*.

a. Infertility*.

b. Small testes.
3. Isolated learning disabilities *#.

Front 6

22q11.2 Syndrome (DiGeorge)

Back 6

A. Genetics.

1. Chromosome microdeletion (Contiguous gene) syndrome.

2. 93% are de novo (new mutations).


B. Clinical Phenotype:
1. Congenital heart disease*.

2. Palate abnormalities (cleft palate or velopalatal insufficiency)*.

3. Thymic hypoplasia (immunodeficiency)*.

4. Hypoparathyroidism with hypocalcemia*.

5. Dysmorphic features:

a. Cleft palate.

b. Broad nose.

c. Triphalangeal thumbs.

d. Wide spaced eyes (hypertelorism).

e. Abnormally shaped ears.
6. Developmental Delay*#.

7. Increased frequency of behavioral or psychiatric disorders*.

Front 7

Williams Syndrome

Back 7

A. Genetics.

1. Chromosome microdeletion (7q11.2).

2. Most are de novo (new mutations).


B. Clinical Phenotype:

1. Congenital heart disease (esp. Supravalvular aortic stenosis)*.

2. Mild Developmental delay (better language skills)*.

3. Loquacious personality.

4. Dysmorphic facial features.

a. Broad mouth.

b. Prominent ears.

c. Small pointed chin.
5. Hypotonia*#.

6. Hypersensitivity/anxiety.

7. Short stature.

8. Calcium abnormalities*.

Front 8

Marfan Syndrome

Back 8

A. Genetics.

1. Autosomal Dominant.

2. Variable expressivity.

3. Fibrillin Gene, Clinical Phenotype.

4. Skeletal.

a. Tall stature.

b. Pectus.

c. Scoliosis*.

d. Loose joints*.

e. Dolichostenomelia (long limbs).

f. Hernias*.

g. Pneumothorax (lung collapse)*.
5. Eyes.
a. Myopia (near sighted).

b. Lens dislocation*.
6. Cardiac.

a. Mitral valve prolapse.

b. Aortic root dilatation risk for dissection*.

Front 9

Achondroplasia

Back 9

A. Genetics.
1. Autosomal dominant, fully penetrant.

2. Most are de novo mutations.

3. Gain of function mutations.

4. FGFR3 mutations.

5. Homozygous mutations lethal.


B. Clinical Phenotype:
1. Rhizomelic short stature.

2. Megalencephaly (large head with frontal bossing).

3. Spinal cord compression*.

4. Normal IQ.

Front 10

Neurofibromatosis

Back 10

A. Genetics.
1. Autosomal Dominant.

2. Variable expressivity.

3. Tumor suppressor gene.

4. Loss of function mutations.

5. Allelic heterogeneity.


B. Clinical Presentation:
1. Café au lait spots.

2. Axillary and inguinal freckling.

3. Cutaneous neurofibromas*.

4. Lisch nodules (iris hamartomas).

5. Plexiform neurofibromas*.

6. Optic gliomas*.

7. Bony lesions*.

8. Mild learning disabilities.

Front 11

Familial Adenomatous Polyposis (FAP)

Back 11

A. Genetics.
1. Autosomal dominant.

2. Tumor suppressor gene.


B. Phenotype:
1. Carpet-like presentation of polyps (>100)*.

2. Extremely high risk for colon cancer by age 40.

3. In persons with mutation, prophylactic colectomy recommended.

4. Upper GI polyps also common*.

Front 12

BRACA

Back 12

A. Genetics.
1. Automsomal dominant.

2. Two identified genes: locus heterogeneity.

3. Variable penetrance.

4. Tumor suppressor gene.

5. Specific mutations common in individuals of Ashkenazi Jewish ancestry.


B. Phenotype:
1. Increased risk for breast and ovarian cancer*.

2. Individuals who have the mutation need increased screening or may elect prophylactic mastecomy and oophorectomy.

3. Male breast cancer with BRCA2 mutations.

Front 13

Li Fraumeni

Back 13

A. Genetics.
1. Autosomal dominant.

2. p53 gene.

3. Tumor suppressor gene.


B. Phenotype:

1. High cancer risk.

2. Soft tissue sarcoma/osteosarcomaLeukemia.

3. Melanoma.

4. Cancer of the colon, breast, pancreas, adrenal cortex, and brain.

5. Poor screening/surveillance.

Front 14

Retinoblastoma

Back 14

A. Genetics.

1. May be due to germline or somatic mutations.

2. In individuals with germline mutations, it is autosomal dominant.

3. Tumor suppressor gene.

4. Classic example of Knudson’s two-hit hypothesis.

5. 90% penetrant.


B. Phenotype:
1. Tumors may be bilateral or unilateral*.

2. All bilateral cases are due to germline mutations.

3. Unilateral cases may be germline or sporadic.

4. Tumors typically present before the age of 5.

5. Increased risk for non-ocular cancers later in life.

Front 15

Huntington Chorea

Back 15

A. Genetics.
1. Triplet repeat expansion of HD Gene (huntington).

2. Autosomal Dominant.

3. CAG, polyglutamine expansion.

4. Anticipation (greater risk for anticipation if paternally inherited).

5. Presymptomatic testing not performed in minors.


B. Clinical Phenotype:
1. Adult onset neurodegenerative disease.

2. Motor disturbances.

3. Cognitive deterioration.

4. Behavioral disturbances.

5. No treatment.