CHROMOSOMAL DISORDERS

Question 1

TRISOMY 13 (PATAU SYN)

Answer 1

microphthalamia: small or poorly developed eyes, cleft lip and/or palate, extra fingers and/or toes

Question 2

TRISOMY 18 (EDWARDS SYN)

Answer 2

IUGR and low birth weight, hand postion (clenched fist and overlapping fingers), small head, jaw, and mouth

Question 3

TRISOMY 21 (DOWN SYN)

Answer 3

Characteristic facies (upslanting palpebral fissures: corners of eyes slanted upwards, flattened appearance of face), single palmar crease, CHD, hypothyroidism, hearing and vision problems, leukemia, Alzheimers, ID, ASD (autism spectrum disorder)

Question 4

XXY (KLINEFELTER

Answer 4

Tall, primary testicular insufficiency&raquo_space; infertile, gynecomastia, genital abnormalities, receptive language skills > expressive language skills, metabolic syn (DM, HTN), Klinefelter variability&raquo_space; the more X the more severe (ID), IS associated with AMA

Question 5

MONOSOMY X (TURNER SYN)

Answer 5

Short stature, premature ovarian failure, infertility, characteristic features (webbed neck, low hairline, lymphedema, kidney problems, CHD&raquo_space; coarctation of aorta, nml intelligence, SHOX gene for bone development and growth, NOT associated with AMA, X is typically maternal in origin

Question 6

XYY (JACOBS SYN)

Answer 6

Subtle; Tall, Learning disabilities, delayed development, behavioral, social, emotional difficulties (ADHD, depression, anxiety, ASD), macrocephaly, macrodontia, ocular hypertelorism: widely spaced eyes

Question 7

47, XXX (TRIPLE X SYN)

Answer 7

Tall, Variable Expressivity: learning disabilities, delayed development, seizures, behavioral and emotional problems, clinodactyly: fifth finger abnml bent or curved, IS associated with AMA

Question 8

TRIPLOIDY

Answer 8

Usually miscarry or don’t live long after birth; those that live longer usually have mosaicism
multiple birth defects (commonly cardiac defects, syndactyly, CNS anomalies)
NOT associated with AMA or advanced paternal age
Dygynic (maternal): asymmetric growth restriction w/ noncystic placenta
Dyandric (paternal): symmetrical growth restriction w/ enlarged cystic placentas&raquo_space; hydatidiform mole (pregnancy called partial molar pregnancy&raquo_space; increased risk for maternal preeclampsia

Question 9

DIGEORGE SYN (22q11.2 DEL SYN)

Answer 9

CHD (tetralogy of Fallot, VSD, PDA), Immune system problems lead to recurrent infections, submucosal cleft palate, bifid uvula, low calcium; Impt genes in deletion include TBX1 (hrt, cleft palate, low calcium levels) and COMT (behavioral problems and mental illness), AD condition but typically not inherited (only 10% of time inherited)

Question 10

PRADER-WILLI SYN

Answer 10

Hypotonia, FTT, Hyperphagia and obesity, behavioral problems, Genetic Mechanism: Mother’s genes turned “off”: 60%-70% Deletion&raquo_space; 5-6 kb del paternal chr15q11.2-13, deletion involves SNRPN gene; 20%-30% maternal UPD (both copies from mother); Imprinting Center Defect: One from mom and one from dad, dad’s “acting” like came from mom (silenced/hypermethylation); Methylation will detect 99%

Question 11

ANGELMAN SYN

Answer 11

Happy demeanor, ataxia, facination with water, seizures, delayed/absent speech, less sleep, Genetic Mechanisms: UBE3A turned “on” in mother: 60%-70% Deletion&raquo_space; 5-7 kb del mat chr15q11.2-13; 11% UBE3A mat del; 3%-7% Pat UPD (both chromsomes from dad); Imprinting Center Defect: One from mom and one from dad, mom’s “acting” like came from dad; Methylation first (detect 80%), then UBE3A sequ and del/dup

Question 12

WILLIAMS SYN (7q-)

Answer 12

Cocktail personality, supravalvular aortic stenosis AKA SVAS (narrowing of aorta), hypercalcemia; ELN gene: Connective tissue and SVAS

Question 13

CRI-DU-CHAT(5p-)

Answer 13

High pitched cat-like cry, intellectual disabilty, microcephaly; 85%-90% de novo, when inherited usually from parents with balanced chromosomal rearrangement

Question 14

WOLF HIRSCHORN SYN (4p-)

Answer 14

Greek warrior helmet: Broad, flat nasal bridge, high forehead, wide-spaced eyes, dolichocephaly: tall narrow skull, prenatally decreased fetal movement; 50%-60% de novo, 40%-45% unbalanced translocation resulting in del of chr4 and trisomy of another chr&raquo_space; de novo or from parent with balanced rearrangement

Question 15

1p36 DEL SYN

Answer 15

Severe ID&raquo_space; absent speech, brain abnormalities (agenesis of the corpus callosum, cerebral cortical atrophy), behavioral problems (self-injury/biting themselves), most de novo, only 20% inherited from unaffected parent

Question 16

CAT EYE SYN (DUP GENETIC MAT FROM CHR22)

Answer 16

About 50% have iris coloboma&raquo_space; “cat eye”, anal atresia, ears (skin tags or holes, or unusually shaped, conductive hearing loss); Genetic Mechanism: Small supernumerary marker chr (sSMC)&raquo_space; usually a dicentric sSMC, ring sSMC; interstitial dup; Best Testing&raquo_space; FISH with Karyotype

Question 17

MILLER DIEKER SYN (17p-)

Answer 17

Lissencephaly: abnl smooth brain; most do not survive beyond childhood, important gene PAFAH1B1&raquo_space; lissencephaly, mostly not inherited (only about 12% of time» balanced rearrangement in parent)

Question 18

WAGR SYN (11p-)

Answer 18

Acronym: Wilms tumor (kidney CA), aniridia, genitourinary (include bicornate “hrt shaped” uterus&raquo_space; prenancy to term difficulties), retardation/intellectual disability, sometimes WAGRO (childhood onset obesity), Genetic Mechanism: Contiguous gene del syn (PAX6, WT1 genes), mostly NOT inherited

Question 19

SMITH MAGENIS SYN (17p-)

Answer 19

Disrupted sleep pattern, distinctive facies (more evident as get older); repetitive self-hugging, hoarse voice, Genetic Mechanism: Del chr17p most common but can also be caused by mutation in RAI1 gene; germline mosacism in mother has been reported