Cytogenetic Conditions Flashcards
How is Pallister-Killian Syndrome usually diagnosed
skin fibroblasts
Incidence of Pallister-Killian Syndrome
5.1/million
Pallister-Killian Syndrome is due to what
supernumerary isochromosome 12p - i(12p)
Pallister-Killian Syndrome is mostly paternal or maternal in origin
maternal
Clinical features of Pallister-Killian Syndrome
sparse anterior scalp hair (usually fills around 5 y.o.)
Hypotonia with contractures
Seizures
II/DD
Streaks of hypo and hyperpigmentation
Coarse facial features that develop with age
HL
Vision impairment
genital abnormalities
CHD
Polydactyly
Cleft palate
Atresia
Lymphedema
Pallister-Killian Syndrome Prognosis
Most don’t survive in utero or postnatal period
Most die because of diaphragmatic hernia or severe CHD
Can reach age 40s
Cri-Du-Chat clinical features
High-pitch cry
microcephaly
micrognathia
abnormal dematoglyphics
broad nasal bridge
epicanthal folds
hypotonia
hypertelorism
low set ears
Round/plump (moon) face
Improper alignment of upper and lower teeth
Short philtrum
Cleft palate or cleft lip
ID/DD
Less frequent:
Heart defect, neurological and renal abnormalities, syndactyly, preauricular tags, hypospadia, cryptorchidism
Cri-Du-Chat incidence
1/20,000-1/50,000
Cri-du-chat prognosis
Most normal life expectancy
If born with life-threatening health issue, 75% die before first month, 90% die before first year
Cri-Du-Chat cytogenetic mechanism
deletion in 5p
80-90% terminal deletions
3-5% interstitial deletions
8-90% due to chromosome breakage during gamete formation in paternal
10-15% due to balanced parental translocation
Cri-Du-Chat Genes
ICE1
ADAMTS16
Wolf-Hirschhorn Syndrome clinical features
facial appearance
seizures
delayed growth and development
ID
Hypotonia
Scoliosis
Kyphosis
CHD
Cleft lip/palate
HL and abnormal pinnae
Malformations in brain and/or urinary tract
Wolf-Hirschhorn Syndrome etiology
deletion in 4p
critical region is 4p16.3
Wolf-Hirschhorn Syndrome incidence
1/20,000-1/50,000
2:1 f:m
87% de novo
- 80% from paternal
13% parents are balanced translocation carrier
13q deletion group 1
proximal with a non-deleted 13q32 band
13q deletion group 2
13q32 band deletion
13q deletion group 3
distal with non-deleted 13q32 band
13q deletion group 1 features
mild to moderate DD and ID
minor anomalies
retinoblastoma
13q deletion group 2 features
one or more major malformations
- microcephaly, brain and eye malformations, distal limb abnormalities, GI tract malformations
Severe ID and DD
13q deletion group 3 features
severe ID and DD
without malformations or physical growth delays
How are most 13q deletions inherited
de novo
carrier rate of rob translocation is 1:1300
9p duplication clinical features
ID
Hypotonia
Microcephaly
Distinctive facial features
skeletal and hand differences
behavioral changes
CNS, cardiac, and kidney findings
Genital development in males
hepatoblastomas, hepatocellular carcinoma, seizures, self-harming bx, dysphagia, lupus erythematosus, and keloids
T9M incidence
1:1,000,000
T9M accounts for what percent of SAB involving T
2.2-2.7%
T9M clinical features
VSD, ASD, Patent ductus arteriosus
Diaphragmatic eventration, neonatal breathing issues, apnea
Cystic dilation of renal tubules, hydronephrosis, calcification, partial duplication, nephrogenic rests, horseshoe kidney
Micrognathia, bulbous nose, low set ears, cleft palate, craniosynostosis
Hemihyperplasia, joint issues, kyphoscoliosis
DD, speech delay
T8M prenatal features
hydronephrosis/bilateral renal pyelectasis
Single umbilical artery
polyhydramnios
agenesis of the corpus callosum
hydrocephalus
high maternal AFP
T8M clinical features
mild to moderate ID
Agenesis of corpus callosum
seizures
cardiac conditions
Cranial and neck folds
Pectus excavatum
Short stature
Scoliosis
Camptodactyly
Underdeveloped nails
missing or small kneecaps
arthrodesis
Meckel diverticulum
Hirschsprung disease
Deep plantar and palmar skin creases
Crytochordism
Unilateral renal agenesis
Urinary reflux
Hypospadias
genital hypoplasia in male
inguinal hernia
hydrocele
Leukemia
T8M sample
extraembryonic mesoderm prenatally
fibroblast postnatally
T8M incidence
1:25,000-1:50,000
4:1 m:f
.1% of all pregnancies
18q deletion incidence
1:55,000
18q deletion genetics
AD
94% de novo
6% mosaic
distal (most common) or proximal
18q deletion distal features
short stature
cognitive impairment
demyelination
midline hypoplasia
18q deletion proximal features
ASD, epilepsy, DD, ID, speech delay
18q deletion clinical characteristics
hypotonia
short stature
deep seated eyes
foot abnormalities
microcephaly
carp shaped mouth
midline hypoplasia
HL
vision issues
genital abnormalities
CHD
Demyelination
Anxiety, depression
Isodicentric 15 clinical characteristics
DD and ID
Psychomotor agitation
Early central hypotonia
Epilepsy
Mild and variable dysmorphic facial features
Isodicentric 15 etiology
chromosome 15q tetrasomy, duplication/inversion 15q
Isodicentric 15 incidence
1:30,000
During a physical exam for T8M, which clinical feature would you be least likely to see that would lead you to this diagnosis?
cleft lip
A supernumerary isodicentric chromosome results from which of the following types of rearrangements?
duplication and inversion
In the case of isodicentric 15 syndrome where symptoms typically include hypotonia, epilepsy, and autism, which phenomenon describes the increased severity of phenotype as more duplications of the Prader-Willi syndrome/Angelman syndrome critical region (PWS/ASCR) are observed in an individual
dosage sensitivity
When testing for Trisomy 8 Mosaicism, the best sample to determine if there are any
cells with Trisomy 8 postnatally is _____ and prenatally is _____
skin biopsy, extraembryonic mesoderm
The proximal section of the 13q arm has been much studied due to its association with… (This is also how 13q deletion syndrome was first discovered)
retinoblastoma
A child is found to have a deletion from 13q13-q14.1. What can be said of genetic testing from here?
It is recommended that parents receive FISH analysis to determine if they have a balanced translocation
A supernumerary isochromosome 12p can cause which of the following conditions
Pallister-Killian Mosaic Syndrome
A 2-month-old with sparse anterior scalp hair, streaks of hyperpigmentation, and
hypotonia was tested by karyotype using peripheral blood. What is an appropriate next
step?
Perform karyotype on skin fibroblasts
An infant is diagnosed with Trisomy 9 Mosaicism (T9M) after an extended NICU
admission. Parental karyotyping is requested, which of the following situations is most
likely to be identified?
T9M of paternal origin resulting from advanced paternal age and a balanced
pericentric inversion of chromosome 9
A child with suspected T9M is being seen in clinic for an initial genetics evaluation.
When conducting the medical history intake, which system is expected to be
phenotypically normal
Hearing
Match the condition with the features
9p duplication
Wolf-Hirschhorn Syndrome
Pallister Killian Mosaic Syndrome
Cri du chat Syndrome
9p duplication - bulbous nose and low-set ears
Wolf-Hirschhorn Syndrome - broad flat nasal bridge and high forehead
Pallister Killian Mosaic Syndrome - sparse scalp hair and folds over the inner corners of the eyes
Cri du chat Syndrome - Small jaw and rounded moon-shaped face
Wolf-Hirschhorn syndrome has wide variability in severity. Which of the following
factors is NOT related to prognosis
size of duplication
An 8-year-old child is evaluated in the pediatrics clinic and is found to have significant speech difficulties, moderate intellectual disability, short stature, microcephaly, distinctive facial features (a prominent nose tip, downslanting palpebral fissures, low-set ears, hypertelorism), brachydactyly, aplasia/hypoplasia of the phalanges, and
hypoplastic nails. For which of the following conditions do you have the highest clinical suspicion
9p Duplication syndrome
What is the correct interpretation of these lab results?
Child: 46,XY,der(21)t(9;21)(p11;p12)
Mother: 46,XX,t(9; 21)(p11; p12)
The child has an unbalanced translocation leading to partial trisomy of 9p and partial monosomy of 21p
that was inherited from their mother, who carries a balanced translocation
An infant presents to the clinic with a high pitched cry, micrognathia, hypertelorism, and they had a low birth weight. You suspect Cri-Du-Chat, and order testing. What do you expect for the results of the test to look like?
A terminal deletion of 5p
What percent of Cri-Du-Chat patients pass away within their first year of life if they are born with life threatening issues ?
90%
