Developmental Genetics

Question 0

Disruptions

Answer 0

Disturbances after an organ has been formed; abnormal structure of an organ or tissue as a result of external forces (not genetics) e.g. Phocomelia (shortened arms or legs) resulting from vascular problems.

Question 1

Malformations

Answer 1

Due to errors occurring in the initial formation of structures, a primary structural defect of an organ or part of an organ e.g. congenital heart abnormalities, cleft lip or cleft palate, polydactyly; most are multifactorial.

Question 2

Deformations

Answer 2

Mechanical distortions, e.g. clubfoot that is caused by lack of amniotic fluid or intra-uterine crowding. They frequently resolve completely soon after birth.

Question 3

Dysplasias

Answer 3

are abnormalities in tissue organization e.g. thanatophoric dysplasia (FGF3R mutation) affects almost all the skeleton; most are monogenic.

Question 4

Sequences

Answer 4

are cascades of effects, e.g. Potter sequence (due to decreased amniotic fluid)

Question 5

Syndromes

Answer 5

groups of anomalies that consistently occur together due to a single underlying cause e.g. down syndrome due to trisomy 21

Question 6

Associations

Answer 6

when traits coincide more often than expected by chance.

Question 7

hypertelorism

Answer 7

Overexpression of SHH can can cause duplication of the morphology.

Question 8

Holoprosencephaly

Answer 8

Mutation in SHH or the Six3 gene (regulator of SHH)

• there is no correlation between a specific mutation in SHHand phenotype (modifier effects)
• a spectrum of defects and disorders
• mild effects: single incisor
• moderate effects: cleft lip and palate
• severe effect: cyclopia

Question 9

Smith-Lemi-Opitz Syndrome

Answer 9

Mutation in 7-dehydrocholesterol reductase

-microcephaly, mental retardation, malformation of mesodermal origin, syndactly and polydactyly

Question 10

Gorlin Syndrome (Nevoid basal cell carcinoma)

Answer 10

Mutation in Patched (Ptch)

• early age basal cell carcinoma (<20 years)
• rib defects

Question 11

Pallister-Hall Syndrome (extremely rare)

Answer 11

Mutation in Gli genes

-brain tumors, polydactyly

Question 12

Rubinstein-Taybi Syndrome

Answer 12

Mutation in CREBBP gene

-broad thumbs and toes, mental disability, short stature, small head, facial features.

Question 13

Thanatophoric Dysplasia

Answer 13

mutation in the extracellular domain and distal tyrosine domain

• SEVERE: similar to homozygous achondroplasia
• usually are still born or die shortly after birth from respiratory distress

Question 14

Achondroplasia

Answer 14

Mutation in transmembrane domain.

• classic dwarfism
• mild to moderate limb shortening, enlarged skull, short and flattened vertebral diskis
• normal life

Question 15

Hypochondroplasia

Answer 15

mutations in the proximal (most common) and distal tyrosine kinase domain

• mild severity
• normal at birth
• normal life

Question 16

46, XX Male Syndrome (de la Chapelle syndrome)

Answer 16

Caused by the translocation of the SRY gene on the Y chromosome as a result of unequal crossing over during meiosis.

• are typical boys and men
• slightly shorter than normal stature
• Normal male genitalia
• 10% show hypospadias
• Mullerian tissue absent
• Infertility

Question 17

46, XY Swyer Syndrome (Pure Gonadal Dysgenesis)

Answer 17

Caused by a loss of Function Mutation of the SRY gene (coding sequence mutation or regulatory sequence)
-Normal female genitalia
-well developed mullerian structures
-Bilateral streak gonads instead of ovaries or testes
-teens show delayed onset of puberty
-Clitoromegaly due to elevated LH
Treatment: removal of streak gonads (avoidance of tumors)
-hormone replacement with estrogen and progesterone

DONOT confuse with Androgen Insensitivity