Biochem CYTOGENETICS AND GENETIC DISORDERS

Down syndrome (trisomy 21): karyotype

47,X*,+21 or 47,XY,+21 (Also: Robertsonian translocation t(14;21))

Down syndrome (trisomy 21): High-yield triggers & features

• Single palmar crease (simian crease)
• Flat facial profile, epicanthal folds
• Duodenal atresia ("double bubble" sign)
• Early-onset Alzheimer's disease (APP gene on Chr 21)
• Atrioventricular septal defect (AVSD)

Down syndrome (trisomy 21): Serum Screening (1st/2nd Trimester)

Quad Screen:
↑hCG
↑Inhibin A

↓AFP
↓Estriol
(Mnemonic: "HI" is elevated)

Edwards syndrome (trisomy 18): Karyotype

47,XX,+18 or 47,XY,+18

Edwards syndrome (trisomy 18): High-Yield Triggers & Features

• Clenched fists with overlapping fingers

• Rocker-bottom feet

• Micrognathia (small jaw) & low-set ears

• Prominent occiput, severe cardiac defects

Edwards syndrome (trisomy 18):Serum Screening (1st/2nd Trimester)

↓ALL markers (AFP, hCG, Estriol, Inhibin A)

Patau Syndrome (Trisomy 13): Karyotype

47,XX,+13 or 47,XY,+13

Patau Syndrome (Trisomy 13): High-Yield Triggers & Features

• Cleft lip / palate

• Holoprosencephaly (failure of forebrain to divide)

• Polydactyly (extra fingers/toes)

• Cutis aplasia (punched-out scalp defect)

Patau Syndrome (Trisomy 13): Serum Screening (1st/2nd Trimester)

↓Beta-hCH

↓PAPP-A

Turner Syndrome: karyotype

45, XO ; Barr bodies: 0

Klinefelter Syndrome: karyotype

47, XXY ; Barr bodies: 1

Double Y / Jacob's: karyotype

47, XYY ; Barr bodies: 0

Turner Syndrome: Key Clinical Triggers

• Female presenting with short stature

• Webbed neck (cystic hygroma) & broad shield chest

• Streak ovaries (primary amenorrhea, elevated LH/FSH)

• Coarctation of the aorta or bicuspid aortic valve

Klinefelter Syndrome: Key Clinical Triggers

• Male presenting with tall stature & long lower extremities

• Gynecomastia & testicular atrophy (small, firm testes)

• Dysgenesis of seminiferous tubules (infertility)

• Low testosterone, elevated LH and FSH

Double Y / Jacob's: Key Clinical Triggers

• Very tall male with severe acne

• Normal fertility and intelligence

Prader-Willi Syndrome

Paternal gene is deleted or mutated (or Maternal uniparental disomy).

Angelman Syndrome

s caused by the loss of functional gene expression on the maternal copy of chromosome 15 (specifically region 15q11-q13)

Prader-Willi Syndrome: triggers

Hyperphagia (uncontrolled eating leading to severe obesity), neonatal hypotonia ("floppy baby"), hypogonadism.

Angelman Syndrome: triggers

Inappropriate laughter ("Happy Puppet"), ataxia, seizures, severe intellectual disability.

Cri-du-Chat Syndrome (5p Deletion): Mechanism

Deletion of the short arm of chromosome 5 (5p minus).

Williams Syndrome (7q Deletion): Mechanism

Microdeletion on long arm of chromosome 7 (includes the elastin gene).

DiGeorge Syndrome / 22q11.2 Deletion (CATCH-22): Mechanism

Microdeletion on chromosome 22q11.2 causing 3rd and 4th pharyngeal pouch dysgenesis.

Cri-du-Chat Syndrome (5p Deletion): Triggers

High-pitched, cat-like cry in infants, microcephaly, ventricular septal defect (VSD).

Williams Syndrome (7q Deletion): Triggers

"Elfin" facial features, extreme friendliness / social personality with strangers, supravalvular aortic stenosis, hypercalcemia

DiGeorge Syndrome / 22q11.2 Deletion (CATCH-22): Mnemonic (CATCH-22)

- Cardiac defects (Tetralogy of Fallot, Truncus Arteriosus)

- Abnormal facies

- Thymic aplasia (T-cell immunodeficiency, recurrent fungal/viral infections)

- Cleft palate

-Hypocalcemia (Parathyroid aplasia →↓PTH)

Rocker-bottom feet + Clenched fists

Edwards Syndrome (Trisomy 18)

Cleft palate + Holoprosencephaly + Polydactyly

Patau Syndrome (Trisomy 13)

High hCG + High Inhibin A (Quad Screen)

Down Syndrome (Trisomy 21)

Female + Webbed neck + Coarctation of aorta

Turner Syndrome (45, XO)

Male + Testicular atrophy + Gynecomastia

Klinefelter Syndrome (47, XXY)

Obesity + Hyperphagia + Paternal Chromosome 15 Deletion

Prader-Willi Syndrome

Happy puppet + Seizures + Maternal Chromosome 15 Deletion

Angelman Syndrome

Hypocalcemia + Absent Thymus + Conotruncal Heart Defect

DiGeorge Syndrome (22q11.2 deletion)