aneuploidies, microdeletions/duplications, and imprinting disorders

RSS features

body asymmetry, triangular facies, fifth finger clinodactyly, macrocephaly, fontal bossing, micrognathia, short stature,

RSS associated genes

CDKN1C, IGF2

1p36 deletion syndrome features

ID/DD, seizures, microbrachycephaly (small, wide head), short and bent fingers and toes, hypotonia

wolf hirschorn syndrome mutation

4p deletion/monosomy 4p

wolf hirschhorn syndrome features

greek warrior helmet face (broad flat nasal bridge and high forehead, widely spaced eyes, short philtrum), ear pits/tags, ID/DD, seizures, microcephaly, genital abnormalities, clefting, ASD

williams syndrome mutation and important gene

7q11.23 deletion, ELN gene

WAGR syndrome mutation and important genes

de novo 11p deletion, WT1 and PAX6

what does WAGR stand for

Wilms tumor, Aniridia (missing colored part of eyes), Genitourinary (undescended testicles or hypospadias), and mental Retardation

jacobsen syndrome mutation

11q deletion

jacobsen syndrome main features

DD/ID, behavioral problems, ADHD, bleeding disorder (platelet disfunction causing easy bruising)

smith magenis syndrome mutation

17p11.2 deletion

hereditary neuropathy w/ liability to pressure palsies mutation and gene

17p deletion PMP22 (same as charcot marie tooth

miller-dieker syndrome mutation

17p deletion

miller-dieker syndrome main features

lissencephaly, ID/DD, seizures, dysmorphic features (sunken middle face, prominent forehead, low set ears), hypotonia

koolen de vries syndrome mutation and important gene

17q del, KANSL1 gene

koolen de vries syndrome main features

DD/ID, cheerful disposition, seizures, hypermobile joints, hypotonia, eye issues (cataracts, optic atrophy, etc), ASD/VSD, kidney issues (pyelectasis, hydronephtosis, etc)

DiGeorge syndrome main feautres

CHD (VSD, ToF, aortic arch, truncus arteriosus), clefting, bifid uvula, immune deficiency, ID/DD, hearing loss, schizophrenia (25%), asymmetric crying face,

cat eye syndrome main features

coloboma (lens/iris/retina defect), anal atresia (no normal anal opening at birth), skin tags/pits, ID/DD

BWS features

omphalocele, macroglossia (large tongue), wilms tumor (nephroblastoma), body asymmetry, neonatal hypoglycemia (low blood sugar), macrosomia (high birth weight)

BWS important genes

IGF2, H19, CDKN1C

Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS) region and chromosome

15q11.2-11.3

smith magenis main features

ID, delayed speech, sleep and behavioral problems, self injury and hugging, licking fingers to flip pages

cat eye syndrome mutation

22q11 duplication

MECP2 duplication syndrome main features

ID/DD, seizures, hypotonia, recurrent infections

in RSS and PWS, there is either missing __________ information or there is a variant on the _________ chromosome

paternal

in BWS and AS, there is either missing ____________ information or there is a variant on the __________ chromosome

maternal

genetic causes of RSS

imprinting defect (35-50%), mat UPD7 (~10%), del/dup involving imprinting center (rare), variant in CDKN1C, IGF2, or other gene near 11p15.5 (rare)

PWS features

hypotonia and feeding issues in infancy followed by excessive eating and obesity in childhood, cognitive impairment, ,behavioral differences (tantrums, stubbornness, OCD), hypogonadism

genetic causes of PWS

4-6Mb deletion (~70%), Mat UPD15 (~25%), imprinting defect (~1%)

BWS and RSS region and chromosome

11p15.5

BWS genetic causes

imprinting defect (imprinting centers 1&2, ~55%), UPD (20%), CDKN1C variant (~10%), microdel/dup (~10%)

AS features

ID/DD, gait ataxia, happy puppet demeanor, microcephaly, seizures

AS genetic causes

5-7Mb deletion (~70%), UBE3A pathogenic mutation (11%), Pat UPD15 (5%), imprinting defect (~4%)

cri-du-chat syndrome mutation

5p deletion

cri-du-chat syndrome features

cat cry, ID/DD, microcephaly, hypertelorism and epicanthic folds

williams syndrome main features

cocktail personality, supravalvular aortic stenosis, elfin facial features, ID, hypercalcemia

hereditary neuropathy w/ liability to pressure palsies features

pes cavus foot deformity (high arch), recurrent neuropathy in a single or multiple nerves, carpal tunnel syndrome

DiGeorge syndrome mutation and gene

90% have de novo 22q11.2 deletion spanning region A-D, TBX1 gene

charcot marie tooth disease main mutation and important gene

17p duplication, PMP22 gene

Charcot marie tooth disease main features

atrophy of muscles in legs, feet, and hands, high arched feet, hammer toes

MECP2 duplication syndrome chromosome

X

MECP2 duplication syndrome mainly effects which sex

males

_________ testing should be offered after identifying a del/dup in a patient

parental

syndromes associated with deletion on the end of a chromosome are more likely to occur when there is a _________ ____________

ring chromosome

what can karyotypes find

structural rearrangements, aneuploidy, large del/dups

FISH can detect __________ at a specific point using a __________

del/dups, probe

microarray can detect large and small __________ but not __________ ___________

del/dups, balanced translocations

t21 ultrasound findings (seen in 50%)

increased NT, absent nasal bone, cardiac anomalies (50%), echogenic bowel, EIF (echogenic intracardiac focus)

t21 features after brith

ID, higher risk of leukemia, high risk of early onset dementia, GI anomalies

how many cases of t21 end in miscarriage

50-75%

the most common translocation that causes 5% of t21 cases is from which chromosomes

14 and 21

90% of t21 cases are in mothers under what age

35

causes of triploidy

2 sperm fertilize 1 egg (most common), diploid sperm/placental anomalies/large and cystic hydaitiform mole, diploid egg

common features of triploidy

MCA, IUGR

most babies who have triploidy are _______

mosaic

t13 ultrasound findings (seen in 90%)

midline facial defects, holoprosencephaly, cardiac defect, polydactyly, clenched hands with overlapping fingers, increased NT

monosomy X ultrasound findings

increased NT, cystic hygroma, horseshoe kidney, coarctation of the aorta, hydrops (fluid build up causing edema)

monosomy x features after birth

short stature, webbed neck, widely spaced nipples, visuospacial deficits, delayed puberty/no periods, streak gonads, infertility (similar to noonan)

what percentage of turner syndrome will end in miscarriage

98%

what percentage of turner syndrome are mosaic

50%

t18 ultrasound findings (90% of cases)

IUGR, increased NT, hypoplastic nasal bone, clenched fists, choroid plexus cyst, cardiac defects, horseshoe kidney

what percent of t18 cases is mosaic or partial t18

5%

what is the most common sex aneuploidy

XXY

what is the most common nonviable aneuploidy

T16

generally, parents with aneuploid pregnancy have what percentage chance of recurrence

1%

XXY features

tall, small testes, gynecomastia, low testosterone, infertility, ID, behavioral differences, increased cancer risks, infertility (due to azoospermia)

what percentage of infertile men have XXY

3%

what percentage of XXY is mosaic

15%