Cytogenetic Conditions Flashcards by Colton Rathbun

How is Pallister-Killian Syndrome usually diagnosed

skin fibroblasts

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Incidence of Pallister-Killian Syndrome

5.1/million

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Pallister-Killian Syndrome is due to what

supernumerary isochromosome 12p - i(12p)

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Pallister-Killian Syndrome is mostly paternal or maternal in origin

maternal

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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

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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

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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

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Cri-Du-Chat incidence

1/20,000-1/50,000

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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

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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

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Cri-Du-Chat Genes

ICE1
ADAMTS16

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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

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Wolf-Hirschhorn Syndrome etiology

deletion in 4p
critical region is 4p16.3

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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

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13q deletion group 1

proximal with a non-deleted 13q32 band

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13q deletion group 2

13q32 band deletion

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13q deletion group 3

distal with non-deleted 13q32 band

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13q deletion group 1 features

mild to moderate DD and ID
minor anomalies
retinoblastoma

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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

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13q deletion group 3 features

severe ID and DD
without malformations or physical growth delays

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How are most 13q deletions inherited

de novo
carrier rate of rob translocation is 1:1300

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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%