Genetics

• 1) 45,X
• 2) 47,XXY
• 3) 47,XY+21

• 1) autosomal dominant
• 2) autosomal recessive
• 3) x-linked recessive
• 4) multifactorial traits

• 1) Beckwith-Wiedemann
• 2) Prader-Willi
• 3) Angelman
• 4) Russel-Silver

Mnemonic: BackWards People Will Always Rule Syria

• 1) Fragile X (large, outside)
• 2) Huntington Disease (modest, inside, late onset)
• 3) Kennedy Disease (modest, inside, late onset)
• 4) The SCA diseases (modest, inside, late onset)
• 5) Myotonic Dystrophy 1/2 (large, outside)
• 6) Friedrich ataxia (large, outside)

Mnemonic: Fathers Hate Kicking Some Mothers

• 1) Gonadal Mosaicism
• 2) Huntingtons
• 3) Neurofibromatosis (cafe au lait spots, neurofibromas)

• 1) Tay Sachs
• 2) Sickle Cell
• 3) Cystic Fibrosis

• 1) Hemophilia A
• 2) Duchenne Muscular Dystrophy

Rickets

• Everywhere except Japanese,
• Korean, Caucasian of Northern European ancestry, First Nations or Inuit should
• be screened

• T1: increased hCG; increased NT; decreased PAPP-A
• T2: increased hCG; increased DIA; decreased AFP; decreased UE3

• 1) Africa
• 2) Mediterranian
• 3) Middle East
• 4) SE asia (parts of india)
• 5) Carribbean
• 6) South America

• a)       Amino acid disorders: e.g. Phenylketonuria (PKU)
• b)       Organic acid disorders: e.g. Methylmalonic acidemia (MMA)
• c)       Urea cycle disorders: e.g. Carbamylphosphate synthetase (CPS) deficiency
• d)      Carbohydrate disorders: e.g. Galactosemia (Classic)

• a)       Glycogen storage disorders: e.g. Glycogenosis type Ia
• b)       Gluconeogenesis defects (rare): e.g. Pyruvate carboxylase deficiency
• c)       Mitochondrial respiratory chain disorders :e.g. Leigh disease
• d)      Fatty acid oxidation disorders: e.g. Medium chain acyl-CoA dehydrogenase (MCAD) deficiency
• e)       Ketone metabolism disorders (rare) e.g. Mitochondrial HMG-CoA Synthase Deficiency

• 1) Lysosomal storage disorders (e.g. Hurlers)
• 2) Peroxisomal Disorders
• 3) Congenital Disorders of glycosylation
• 4) Inborn errors of control synthesis

• expect to see in several generations
• an affected person will have an affected parent
• each offspring has a 50% chance of inheriting trait
• males and females transmit equally

• expressivity: is the severity of the expression at the phenotype level, different types of expression
• penetrance: the probability that a gene will have any expression (looking at a population level)

• mainly males affected
• no male to male transmission
• all daughters of an affected male are carriers
• each son of a carrier female has a 50% chance of being affected
• each daughter of an carrier female has a 50% chance of being affected

• Each daughter has a 50% chance of being affected if mom is affected
• no male to male transmission
• each daughter of a male carrier will be affected
• each son of an affected female has a 50% chance of being affected

• If trait appears in family pedigree, it is generally only in siblings
• affects males and females in equal numbers
• 25% recurrence risk if both parents are carriers
• more suspicious if there is consanguinuity

1.Recurrence risk is higher if more than one family member is affected.

2.The greater the severity, the higher the recurrence risk.

3.Recurrence risk is greater if the proband is of the less commonly affected gender.

4.Recurrence risk decreases rapidly in more distantly related individuals.

5.Recurrence risk for first degree relatives is approximately the square root of the population incidence of the trait.

• 1) problems of early growth/development
• 2) still births and neonatal deaths
• 3) fertility problems
• 4) family history of genetic problems
• 5) prenatal diagnosis
• 6) neoplasia (formation of new tissue)

• peripheral blood (most common);
• umbilical cord blood (cordocentesis)
• fibroblasts (skin biopsy)
• amniocytes (amniocentesis)
• chorionic villi (chorionic villus sampling)

• gowers sign
• late walking
• Elevated creatine kinase
• multiplex PCR first, looking for a bum dystrophin gene (large deletions).

• Advanced maternal age
• previous stillbirth/livebirth with chrom. abnormality
• family history of chrom. abnormality
• family history of single gene abnormality
• family history of x-linked recessive
• abnormal pregnancy screening or ultrasound
• test tube baby
• risk of NTD
• moaisism

• single transverse palmar crease
• Clinodactyly
• Hypertelorism (increased distance between organs)

• 1) Deformation (due to mechanical deformation, e.g. club feet)
• 2) Disruption (interference with an originally normal developmental process, FAS)
• 3) Dysplasia (abnormal organization of cells into tissues, achondroplasia)
• 4) Malformation (due to an intrinsically abnormal development process, cleft lip and palate)

• 1) Sequence (pattern of anomalies derived from a single defect, oligohydraminos)
• 2) Developmental Field Defect (disturbed development of a related group of cells, limb-body wall complex)
• 3) Syndrome (recognized pattern of anomalies that has a unique set of symptoms, Down's)
• 4) Association (related, but we don't know why, VATER association)

• Vertebral defects
• Anal atresia
• TE fistula
• Radial/Renal dysplasia

• Nuchal skin
• single crease
• brachycephaly
• congenital heart defects
• usually sterile men

• Edwards
• semilethal, only 50% make it past the first week
• more than 6 arches

• patau syndrome
• most dont last a month
• polydactyly