ABGC Chromosomal Conditions

Triploidy - 3 Key Symptoms

Growth restriction, CNS Involvement +seizures, Omphalocele

Trisomy 13 (Patau) - 3 Key Symptoms

Polydactyly (usually postaxial), Holoprosencephaly +cleft lip/palate, Congenital Heart Defects (VSD/ASD/PSD), sometimes omphalocele

Trisomy 18 (Edward) - 3 Key Symptoms

OMPHALOCELE and Head abns. (Microcephaly +Holoprosencephaly +Cleft lip/palate +micrognathia (small jaw)), Club foot/Rocker bottom feet, Congenital Heart Defects (VSD/ASD/PDA)

Trisomy 21 - 3 Key Symptoms

Distinct facies +cleft lip/palate; Intellectual/Developmental Deficits/Delays; Congenital Heart Defects (VSD/ASD/PDA), sometimes omphalocele

Klinefelter Syndrome - 3 Key Symptoms

Tall stature, Delayed/Incomplete Puberty +infertility, Higher Risk for Osteoporosis and Male Breast Cancer

Turner Syndrome - 3 Key Symptoms

Short stature, Heart/Kidney abns. (horseshoe kidney, coarctition of aorta (narrow aorta)), Delayed/Incomplete puberty +infertility +streak gonads in XY mosaics (risk for Gonadoblastoma)

22q11.2 Deletion Syndrome (VeloCardioFacial, DiGeorge) - 3 Key Symptoms

Distinct Facies (Facial) +cleft palate (Velo), Congenital Heart Defect (Cardio) (Tetrology of Fallot), Immune deficiency

Angelman Syndrome - 3 Key Symptoms

CNS Involement +Seizures +Cerebral involvement (tremor, balance issues), Behavior Abns. (Happy Demeanor, Less Sleep), Microcephaly

Cri-du-Chat Syndrome - 3 Key Symptoms

High pitched cat-like cry; Head Abns. (Microcephaly, Micreognathia, Hypertelorism), CNS Involvement

Prader-Willi Syndrome - 3 Key Symptoms

Low infant appetite followed by Hyperphagia in childhood +DM2; CNS Involvement +Behavior Abns. (tantrums), Infertility

Smith-Magenis Syndrome - 3 Key Symptoms

CNS Involvement +Behavior Abns. (self-injury, tantrums); Sleep issues (low melatonin production); Distinct Facies (M shaped mouth, hypertelorism/brachycephaly (short head))/Skeletal abns (short stature, scoliosis)

Williams Syndrome - 3 Key Symptoms

Distinct Facies (wide mouth); CNS Involvement +Behavior Abns. (Highly social/trusting), Congenital Heart Defects (Artery Stenosis (SVAS, PS))

Wolf-Hirschhorn Syndrome - 3 Key Symptoms

Distinct Facies (hypertelorism, fish mouth, flat nose bridge (Greek Helmet), ear tags) +cleft lip/palate +microcephaly, CNS Involvement +Seizures, Growth restriction +short stature +scoliosis +hypotonia

Beckwith-Wiedemann Syndrome - 3 Key Symptoms

Overgrowth +hemihyperplasia/asymmetry +increased risk for Wilms tumor; neonatal hypoglycemia; Omphalocele

Russel-Silver Syndrome - 3 Key Symptoms

Growth restriction + asymmetry +short stature +normal head size; Distinct facies (triangular head); CNS involvement; can also have hypoglycemia due to low fat reserves

Triploidy - Prenatal Findings

In mother: Polyhydramnios, can lead to partial molar pregnancy (when third set is inherited from father, Diandric) -> risk of cancer to mother and SAB; In Baby: IUGR with big head (digynic only), omphalocele

Triploidy - Genetics and Inheritance

De novo; 80% due to dispermy, can also be due to: failure to extrude 2nd polar body in oogenesis, Diandric (diploid sperm) = partial molar pregnancy SAB @ 20w, Digynic (diploid egg) = non-molar pregnancy SAB @ Tri3

Triploidy - Onset and Progression

Not compatible with life unless mosaic; Usually Late Tri2/Tri3 SAB

Trisomy 13 (Patau) - Prenatal Findings

In Mother: All normal values (or normal with low bHCG) on Quad Screen; In baby: IUGR, Median CL/CP, postaxial polydactyly, increase NT in Tri1, single umbilical artery, omphalocele

Trisomy 13 (Patau) - Genetics and Inheritance

(47, XY or XX, +13) De novo or inherited unbalanced translocation from parent with balanced translocation or Robertsonian translocation

Trisomy 13 (Patau) - Onset and Progression

Can lead to live birth, often live 7-10 days after birth, 10% survive past 1y

Trisomy 18 (Edward) - Prenatal Findings

In Mother: Quad screen shows all values low; In Baby: Increased NT, OMPHALOCELE, Choroid Plexus Cysts (hyperechoic mass in brain), CL/CP, Club foot/rocker bottom feet

Trisomy 18 (Edward) - Genetics and Inheritance

(47, XY or XX, +18) De novo or inherited unbalanced translocation from parent with balanced translocation

Trisomy 18 (Edward) - Onset and Progression

Can lead to liver birth, often live 5-15 days after birth,

Trisomy 21 - Prenatal Findings

In Mother: Quad screen shows Low AFP, High bHCG, low estradiol, and high Inhibin (opposite normal); In Baby: absent nasal bone, LARGE NT/Cystic Hygroma, hyperechoic bowel/duodenal atresia, ventriculomegaly (fluid in brain ventricles), short long bones, CL/CP, Renal Pyelectasis (large kidney ureter), heart defect (needs fetal echo), omphalocele

Trisomy 21 - Genetics and Inheritance

(47, XY or XX, +21) De novo or inherited unbalanced translocation from parent with balanced translocation or Robertsonian translocation

Trisomy 21 - Onset and Progression

Reduced lifespan (60y) due to CHD and premature aging/early onset Alzheimer's (40-50y)

Klinefelter Syndrome - Genetics and Inheritance

(47, XXY) de novo, can be (46, XY/47, XXY) mosaic (15%) or have extra X chromosomes (48,XXXY) etc. with increased severity, usually due to Meiotic 1 nondisjunction

Klinefelter Syndrome - Onset and Progression

Not detected until infertility concerns historically

Turner Syndrome - Genetics and Inheritance

(45, X) de novo, can be isochromosome (46, X, i(Xq)) (15%) or mosaic (45, X/46, XX) (15%), Usually due to Meiotic (1 or 2) nondisunction or Mitotic nondisjunction/anaphase lag. NOT ASSOCIATED WITH AMA.

Turner Syndrome - Prenatal Findings

In Mother: nothing; In Baby: Large NT (most common aneuploidy cause of large NT), aorta abns., horseshoe kidney

Turner Syndrome - Onset and Progression

Historically not detected until puberty, normal lifespan

22q11.2 Deletion Syndrome (VeloCardioFacial, DiGeorge) - Genetics and Inheritance

Deletion of 22q11.2, de novo, 10% are AD inherited

22q11.2 Deletion Syndrome (VeloCardioFacial, DiGeorge) - Prenatal Findings

In Mother: nothing; In Baby: CHD (tetrology of fallot), Large NT (most common CNV cause of Large NT)

22q11.2 Deletion Syndrome (VeloCardioFacial, DiGeorge) - Onset and Progression

40-50y avg. lifespan, due to thymus/immune deficiency or CHD complications

Angelman Syndrome - Genetics and Inheritance

LACK OF MAT. Deletion of maternal 15q11-13, Paternal Uniparental Disomy of c15, mutated imprinting center in PWS region such that it is imprinted like a paternally inherited copy, or mutation of UBE3A gene. Most commonly due to deletion of maternal copy.

Angelman Syndrome - Onset and Progression

Normal life expectancy due to condition stability, but highly dependent due to motor instability

Prader-Willi Syndrome - Genetics and Inheritance

LACK OF PAT. Deletion of paternal 15q11-13, Maternal Uniparental Disomy of c15, or mutated imprinting center in PWS region such that it is imprinted like a maternally inherited copy. Most commonly due to deletion of paternal copy.

Prader-Willi Syndrome - Onset and Progression

20-30y avg. lifespan, usually due to respiratory issues or DM2 complications

Cri-du-Chat Syndrome - Genetics and Inheritance

5p15.2-15.3 deletion, 90% de novo or can be due to an inherited unbalanced translocation (5 pads on a cat paw)

Cri-du-Chat Syndrome - Onset and Progression

Normal lifespan, due to most syndrome-related deaths happening in infancy due to pneumonia or severe organ defects

Smith-Magenis Syndrome - Genetics and Inheritance

17p11.2 deletion or AD; RAI1 gene mutation, usually de novo (reduced penetrace, can be inherited from unaffected parent, AD)

Smith-Magenis Syndrome - Onset and Progression

So rare there isn't an average lifespan, but documented cases of individuals living into 80's

Williams Syndrome - Genetics and Inheritance

7q11.23 deletion, de novo only

Williams Syndrome - Onset and Progression

60-70y lifespan, usually death due to heart and blood vessel issues (HTN)

Wolf-Hirschhorn Syndrome - Genetics and Inheritance

4p16.3 deletion, all are de novo for due to inheritance of an unbalanced translocation (4 letters in Wolf)

Wolf-Hirschhorn Syndrome - Onset and Progression

Most pass within 2y, some live into middle ages, usually pass due to complex seizure complications, CHD's, or respiratory infections

Beckwith-Wiedemann Syndrome - Genetics and Inheritance

GAIN OF PAT, LOSS OF MAT. Located at 11p15; Due to: Paternal Uniparental Disomy of c11, Duplication of Paternal 11p15, Loss of Mat methylation on IC2 -> hypomethylation of DMR2, Gain of Mat Methylation on IC1 -> Hypermethylation of DMR1, Maternal copy CDKN1C loss - Needs Methylation, del/dup, and UPD testing

Russel-Silver Syndrome - Genetics and Inheritance

Maternal c7 Uniparental Disomy and Epigenetic changes that alter gene expression in 11p15.5 region - Needs Methylation, del/dup, and UPD testing

Beckwith-Wiedemann Syndrome - Onset and Progression

Typically normal, may pass in early years due to untreated hypoglycemia and Wilms Tumor/hepatoblastoma

Russel-Silver Syndrome - Onset and Progression

Normal lifespan, just watch for hypoglycemia due to feeding difficulties and low body fat