6/10/25 Inheritance patterns and common genetic syndromes

Question 1

Define pleiotropy

Answer 1

the property of a single gene to have multiple effects

Question 2

What is when one clinical disease is caused by variants in different genes

Answer 2

Locus heterogeneity

Question 3

What occurs when 2 different types of variant alleles are present.

Answer 3

Compound heterozygous

Question 4

What inheritance pattern is seen in every generation?

Answer 4

Autosomal Dominant

Question 5

In what inheritance pattern are affected individuals usually seen in only one generation?

Answer 5

Autosomal recessive

Question 6

Why are females more affected than males in x linked dominant disorders?

Answer 6

Typically more lethal in males

Question 7

Why are X-linked recessive disorders much more common in males vs females?

Answer 7

Only need to inherit the affected allele to be symptomatic

Question 8

What type of inheritance pattern leads to hypertropic cardiomyopathy?

Answer 8

Autosomal dominant

Question 9

Genes in Hypertropic cardiomyopathy

Answer 9

MYH7 and MYBPC3

Question 10

Unique characteristics of hypertropic cardiomyopathy

Answer 10

Penetrance is age dependent
Variability expressivity

Question 11

What type of inheritance pattern results in CF?

Answer 11

Autosomal recessive

Can be homozygous or compound heterozygous

Question 12

CF gene

Answer 12

CFTR (delta-F508 problematic allele)

Question 13

CF symptoms

Answer 13

Chronic sinopulmonary disease, pancreatic insufficiency, GI abnormalities, male infertility, salt loss

Question 14

What type of inheritance pattern results in Rett Syndrome?

Answer 14

X linked dominant

Lethal in XY

Question 15

Rett syndrome gene

Answer 15

MECP2

Question 16

Rett syndrome symptoms

Answer 16

Neurodevelopmental disorder

Stereotypic hand movements
Loss of spoken language
Gait abnormalities

Question 17

What type of inheritance results in DMD (Duchenne muscular dystrophy)?

Answer 17

X linked recessive

Question 18

DMD gene

Answer 18

DMD

Question 19

DMD symptoms

Answer 19

Onset at age 6, death by 3rd decade of life

Delayed milestones, progressive muscle disease, cardiomyopathy, respiratory failure

Question 20

What is variable penetrance

Answer 20

individuals with the same genotype (genetic makeup) may or may not express the associated phenotype (observable trait).

Question 21

What is expressivity

Answer 21

refers to the degree to which a genotype is expressed as a phenotype within an individual. It describes the variation in how a particular trait or condition is manifested in people who carry the same gene variant. Essentially, it’s about the “strength” or “intensity” of the phenotype

Question 22

What is a carrier?

Answer 22

someone who is heterozygous for a pathogenic, recessive allele. They carry a variant gene, but they are not affected by it, nor do they express it phenotypically.

Question 23

What should be noted when taking a family hx?

Answer 23

Go back 3 generations

Cause and age of death
Ancestry on both sides of family
Note any chronic conditions, disease diagnoses, congenital abnormalities, and intellectual or developmental delays

Question 24

Balanced vs unbalanced structural abnormalities

Answer 24

Balanced: reproductive risk (translocation, inversion, insertion)

Unbalanced: Copy number variant, risk for “carrier” (deletion, duplication)

Question 25

Trisomie 21 inheritance

Answer 25

95% free-standing trisomy, 5% mosaicism, translocation, etc.

Question 25

Symptoms of down syndrome

Answer 25

Intellectual disability, heart defect (50%), obstructive sleep apnea (>50%), otitis media (>50%), hypotonia, facial features (flat nasal bridge, facial profile/low set ears/upslanting palpebral fissures; epicanthal folds), short neck w/ loose skin at nape (nuchal redundancy), broad hands w/ single palmar crease, clinodactyly

Question 26

Down syndrome testing

Answer 26

Karyotyping. Important to know if robertsonian translocation is present because it can increase the reoccurance risk

Question 27

Symptoms of trisomie 18

Answer 27

Early lethality, intrauterine growth restrictions, congenital heart defects, abnormal faces, microcephaly, micrognathia, hypertonia, clenched hands, rocker bottom feet, low set ears

Question 28

Edward syndrome testing

Answer 28

Karyotyping, chromosomal analysis

Question 29

Trisomie 13 symptoms

Answer 29

Early lethality, CNS, midline defects (holoprosencephaly, bilateral cleft lip/palate, scalp defects, omphalocele), post axial polydactyly, hypotelorism/microphthalmia, congenital heart defects

Question 30

Patau syndrome testing

Answer 30

Karyotyping, chromosome analysis

Question 31

What causes turner syndrome?

Answer 31

Missing X chromosome. Only viable in females

Question 32

Turner syndrome symptoms

Answer 32

Short stature, broad/shield-shaped chest, congenital heart defects, renal anomalies, primary amenorrhea, broad webbed neck, low posterior hairline

Question 33

Turner syndrome testing

Answer 33

Karyotyping, chromosome analysis (half are 45, X other half are mosaic)

Question 34

Turner syndrome staging

Answer 34

prenatal=cystic hygroma neonatal=edema, nuchal thickening pediatric=short stature adult=primary amenorrhea/infertility

Question 35

What causes klinefelter syndrome?

Answer 35

Extra X chromosome (47,XXY), lethal in females

Question 36

XXY symptoms

Answer 36

Infertility (azoospermia/small testes), taller than avg, gynecomastia (increased risk of breast cancer)

Question 37

XXY testing

Answer 37

Karyotyping, chromosome anaysis

Question 38

47 XXX symptoms

Answer 38

subclinical, associated w/ tall stature/mild delays (motor/speech/language), seizure, kidney abnormalities

Question 39

Inheritance of marfan syndrome

Answer 39

Autosomal dominant Connective tissue disorder

Question 40

Marfan syndrome gene

Answer 40

FBN1

Question 42

How can marfan syndrome be diagnosed with family hx?

Answer 42

First degree relative AND Ectopia lentis, systematic score ≥ 7, aortic root enlargement

Question 42

How can marfan syndrome be diagnosed without family hx?

Answer 42

Aortic root enlargement AND 1 other: Pathogenic FBN1 variant, ectopia lentis, systematic score ≥ 7

Question 42

Ehlers Danlos syndrome inheritance

Answer 42

Autosomal dominant

Question 43

Ehlers danlos syndrome genes

Answer 43

COL5A1, COL5A2

Question 43

Ehlers danlos syndrome symptoms

Answer 43

Connective tissue disorder -> soft/velvety/hyperextensible skin, large/small joint hypermobility, easy bruising, atrophic scars

Question 43

How are monogenic disorders tested for?

Answer 43

Sanger sequencing

Question 44

How are chromosomal syndromes tested for?

Answer 44

Karyotyping, chromosomal analysis

Question 45

How is neurofibromatosis 1 inherited

Answer 45

Autosomal dominant

Question 45

COL1A/2 Related osteogenesis Imperfecta inheritance

Answer 45

Autosomal dominant

Question 45

Neurofibromatosis 1 gene

Answer 45

NF1

Question 45

Neurofibromatosis 1 symptoms

Answer 45

Café-au-lait spots, axillary/inguinal freckling, cutaneous neurofibromas, lisch nodules (iris hamartomas, plexiform neurofibromas, optic glioma, osseous lesion

Question 46

COL1A1/2 related osteogenesis imperfecta symptoms

Answer 46

Bones fractures, dentinogenesis imperfecta (opalescent teeth), hearing loss (adults), blue sclera, deafness, ligamentous laxity, skin abnormalities, scoliosis

Question 47

Achondroplasia inheritance

Answer 47

Autosomal dominant with complete penetrance

Question 48

Achondroplasia gene

Answer 48

FGFR3

Question 49

Achondroplasia symptoms

Answer 49

Disproportionately short limbs (rhizomelic short stature), short fingers with “trident” configuration, enlarged head, depressed nasal bridge, constricted chest, craniocervical jxn issues

Question 50

Achondroplasia life expectancy

Answer 50

Normal. Most widely recognized skeletal dysplasia