Developmental Genetics Flashcards
Disruptions
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.
Malformations
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.
Deformations
Mechanical distortions, e.g. clubfoot that is caused by lack of amniotic fluid or intra-uterine crowding. They frequently resolve completely soon after birth.
Dysplasias
are abnormalities in tissue organization e.g. thanatophoric dysplasia (FGF3R mutation) affects almost all the skeleton; most are monogenic.
Sequences
are cascades of effects, e.g. Potter sequence (due to decreased amniotic fluid)
Syndromes
groups of anomalies that consistently occur together due to a single underlying cause e.g. down syndrome due to trisomy 21
Associations
when traits coincide more often than expected by chance.
hypertelorism
Overexpression of SHH can can cause duplication of the morphology.
Holoprosencephaly
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
Smith-Lemi-Opitz Syndrome
Mutation in 7-dehydrocholesterol reductase
-microcephaly, mental retardation, malformation of mesodermal origin, syndactly and polydactyly
Gorlin Syndrome (Nevoid basal cell carcinoma)
Mutation in Patched (Ptch)
- early age basal cell carcinoma (<20 years)
- rib defects
Pallister-Hall Syndrome (extremely rare)
Mutation in Gli genes
-brain tumors, polydactyly
Rubinstein-Taybi Syndrome
Mutation in CREBBP gene
-broad thumbs and toes, mental disability, short stature, small head, facial features.
Thanatophoric Dysplasia
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
Achondroplasia
Mutation in transmembrane domain.
- classic dwarfism
- mild to moderate limb shortening, enlarged skull, short and flattened vertebral diskis
- normal life
Hypochondroplasia
mutations in the proximal (most common) and distal tyrosine kinase domain
- mild severity
- normal at birth
- normal life
46, XX Male Syndrome (de la Chapelle syndrome)
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
46, XY Swyer Syndrome (Pure Gonadal Dysgenesis)
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
