Genetics/Embryology Flashcards
Pleiotropy
- Instances where multiple, seemingly unrelated phenotypic manifestations, often in different organ systems, result from a single genetic mutation
- Exhibited by most syndromic genetic illnesses
- Such as homocystinuria
What is the pathogenesis of Homocystinuria?
- Autosomal recessive mutation
- Due to Cystathionine Synthetase deficiency
- Unable to form Cystathione from Homocysteine
- Methionine is unable to be converted to homocysteine and then to Cysteine
- Cysteine becomes essential amino acid
What are the clinical findings in Homocystinuria?
- Optic lens dislocation (Ectopia Lentis)
- Intellectual disability
- Marfanoid habitus
- Thromboembolic complications
How do you diagnose Homocystinuria?
Increased plasma and urinary homocystine levels
What is the treatment for Homocystinuria?
- Pyridoxine (B6) administration
- Dietary methionine restriction & cysteine supplementation
What causes Patau syndrome?
- Trisomy 13
- Karyotype 47, XX
- Results from meiotic nondisjunction or failure of chromosomal separation during meiosis.
- Causes inheritance of a chromosome pair from one parent rather than a single chromatid
- Maternal age >35 increases oocyte division abnormality
- Most die in utero, only 5% survive after birth
What is the pathophysiology of Patau syndrome?
- Defect in the fusion of the prechordal mesoderm
- Affects the growth of the mid face, eyes and forebrain
Physical presentation of Patau syndrome?
Catastrophic midline defects including:
- Holoprosencephaly
- Microcephaly
- Microphthalmia
- Cleft lip/palate
- Omphalocele
- Abnormal brain development results in intellectual disability and seizures
- Polydactyly and cutis aplasia are other findings
Turner Syndrome
- 45, X karyotype
- Due to loss of paternal X chromosome
- Neonates have lymphedema and cystic hygroma due to coarctation of the aorta.
- Short stature, primary amenorrhea, bicuspid aortic valve, horseshoe kidney, webbed neck, broad chest and widely spaced nipples are other features
Holoprosencephaly
Embryology
- Incomplete division of the forebrain (prosencephalon) into two hemispheres
Etiologies
- Genetic causes are trisomy 13 or sonic hedgehog mutations
- Environmental causes are maternal alcohol use
Clinical features
- Leads to developmental field defect
- Mild: closely set eyes (hypotelorism), cleft lip/palate
- Severe: single midline eye (cyclopia), primitive nasal structure (proboscis), midfacial clefts
When does cleavage of the prosencephalon into the telencephalon and diencephalon normally occur?
5 weeks gestation
What is developmental field defect?
When an initial embryonic disturbance leads to multiple malformations by disrupting the development of adjacent tissues and structures within a region
Edwards Syndrome
- Trisomy 18
- Due to meiotic nondisjunction
- Karyotype 47, XX
- Increased risk due to maternal age >35
- Micrognathia, low set ears, prominent occiput and rocker bottom feet
- Significant hypertonia, clenched hands with overlapping fingers,
- Cardiac anomalies include ventricular septal defect, patent ductus arteriosus
- Genitourinary symptoms include horsehoe kidney
- GI anomalies include meckel’s diverticulum or malrotation
- Prenatal ultrasound may show restricted growth
- Most die in utero and some live up to 2 years
- Surviving patients have severe intellectual disability
What is Cri-du-chat syndrome?
- Due to 5p deletion
- Presents with weak cat-like cry
- Hypotonia, failure to thrive and developmental delay
- Phenotypic features include microcephaly, low set ears, hypertelorism (long orbit distance) and broad nasal bridge
What is DiGeorge syndrome?
- Due to 22q11 deletion
- Aortic arch anomalies
- Thymic hypoplasia/aplasia
- Hypocalcemia (parathyroid gland underdevelopment)
- Hypertelorism, low set ears, micrognathia and cleft palate
Down syndrome
- Trisomy 21
- Most common autosomal trisomy
- Classic findings are flat facial profile, upslanting palpebral fissures, low set small ears, single transverse palmar crease and hypotonia
Infant with oral thrush, interstitial pneumonia and severe lymphopenia during the first year of life is consistent with what?
Vertical transmission of HIV-1
What is the risk of HIV infection in infant born to an HIV-positive mother who received no prenatal antiretroviral therapy (ART) vs one that received ART?
35% vs 1-2%
Which ART should be avoided due to teratogenic risks?
Efavirenz in first 8 weeks
What is heteroplasmy? And how is it explained?
- When some cells have completely healthy mitochondria and others contain mitochondria affected by genetic mutation
- Explained by the random distribution of normal and mutated mitochondria between daughter cells during mitosis
The dorsal pancreatic bud forms the _____, _____, _____ and _____.
Tail, body, head and accessory pancreatic duct
The small ventral pancreatic bud forms the _____, _____ and the _____.
uncinate process, part of the head and the proximal portion of the main pancreatic duct
What is pancreatic divisium?
What are the signs?
- When the dorsal and ventral parts fail to fuse at 8 weeks gestation
- Asymptomatic but may cause chronic abdominal pain and/or pancreatitis.
