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
