Chromosomal Disorders Flashcards by Keri Ramsey

What are the major anomalies in the newborn stage of Trisomy 21?

Heart defect
Duodenal atresia
Hirschsprung Disease

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What labs are abnormal in the newborn stage of Trisomy 21?

Transient myelopoiesis
(20-30% risk leukemia)
Hypothyroidism

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What are the heart anomalies in Trisomy 21?

Heart (50%)
* AV Canal (AVSD) (40%)
* VSD (32%)
* ASD (10%)
* Tetralogy of Fallot (6%)

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25-40% of children with duodenal atresia have what disorder?

Trisomy 21

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12% of patients with Hirschprung have what disorder?

Trisomy 21

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What are the physical findings in Trisomy 21?

Low tone
Microcephaly
Brachycephaly
Upslanting palpebral fissures
Epicanthal folds
Flat nasal bridge
Tongue thrusting
Small cupped ears
Redundant nuchal (neck) skin
Single palmar crease & clindoactyly
Sandal gap or proximally placed toes

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What are complications of Trisomy 21 over time?

Frequent ear infections with conductive hearing loss (82%)
Risk of autoimmune disorders–Thyroid
Celiac disease
Respiratory infections & immunodeficiency
Leukemia 2-3% (if no transient disorder)
Visual problems (56%)
Atlanto-axial instability (base of skull to spine)
Developmental delay. Will need all therapies (occupational,
physical, speech)

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What are complications of Trisomy 21 in the adult?

Premature Alzheimer’s in adults (age 40)
Males often infertile
Females are subfertile (15-30% fertile)
Risk of Trisomy 21 in offspring 35-50%.

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What is the incidence of Trisomy 21 in a 35 year-old pregnant person?

1 in 350

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What is the incidence of Trisomy 21 in a 40 year-old pregnant person?

1 in 100

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What percentage of nondisjunction occurs in meiosis I in Trisomy 21? Meisois II?

77% meiosis I, 23% meiosis II

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What percentage of Trisomy 21 is due to a Robertsonian translocation?

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What percentage of Trisomy 21 is mosaic?

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What is the recurrence rate of T21 with a Robertsonian translocation?

Empirically derived
* t(14:21) 10-15% mother, <5% father

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What is the recurrence risk of 21q21q isochromosome?

100%

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Is T18 due to nondisjunction in Meiosis I or II?

majority Meiosis II

What percentage of T18 are mosaic?

What percentage of T18 are due to translocations or partial duplication?

~1%

What is the prognosis for T18?

Poor. 90% will die by age 1, regardless of intervention

What are the clinical findings of T18?

Everything is small
1/3 are premature, 38% die during labor
Characteristic craniofacial features
Overriding fingers (contractures)
Nail hypoplasia
Short hallux
Rocker bottom feet
Short sternum
Major internal malformations
Heart defect = 90% (VSD, multiple valve
anomalies)

What are the major anomalies in T18?

Heart defects:
Respiratory: Laryngomalacia, trachoebronchomalacia, apnea, pulm. HTN
Ophthalmology: 10% with cataract, corneal opacities. Photophobia is common
Small, simple ears, small ear canal. Mod-severe sensorineural hearing loss
Limb anomalies: 5-10%, radial aplasia, club foot
Scoliosis common in older children
Horseshoe kidney in 2/3. UTI’s more common
Increased risk for neoplasia: Wilms tumor (1% risk), hepatoblastoma. Average age 5,
from 12 month to 13 years
Brain anomalies in 5%
Seizures in 25-50%

What are the hallmark features of Trisomy 13?

HOLOPROSENCEPHALY!
CUTIS APLASIA
Polydactyly
Renal anomalies
Eye anomalies (anophthalmia,
microphthalmia)

What are the prenatal findings in Turner syndrome?

Hydrops, cystic hygroma, heart defect

What are the physical features of Turner syndrome?

Webbed neck
Downslanting eyes
Low set ears, posteriorly rotated
Wide chest (shield chest, wide
spaced nipples)
Puffy hands and feet (edema)
Hyperconvex nails

What are the older presentations of Turner syndrome?

Short stature * SHOX deficiency * Madelung deformity (radius shortened) * Responsive to growth hormone Streak gonads--> amenorrhea and lack of pubertal development * Endocrinology referral for sexual development * Subfertility to infertility is typical * Premature ovarian failure Hypothyroidism: Yearly thyroid testing

What are features of Klinefelter syndrome?

Hypergonadotropic hypogonadism * Pituitary function normal, nonresponsive testes * Male factor infertility Tall stature (extra SHOX copy) Low tone Some difficulties in school related to reading and language Problems with emotional regulation

What is the genetic change in Wolf-Hirschhorn?

Del 4p15.3

What are findings that are present in over 75% of individuals with Wolf-Hirschhorn?

* IUGR/postnatal growth deficiency * *Intellectual disability— absent speech * Hypotonia * Muscle hypertrophy * *Seizures * Feeding difficulties * Abnormal ears

What are findings that are present in 50-75% of individuals with Wolf-Hirschhorn?

* Distinctive EEG abnormalities * Skeletal anomalies * Craniofacial asymmetry * Abnormal teething * Ptosis * *Antibody deficiency

What are findings that are present in 25-50% of individuals with Wolf-Hirschhorn?

* *Heart defects * Hearing defects * *Eye/optic nerve defects * *Cleft/lip palate * Stereotypies * Structural brain anomalies * Genitourinary tract defects

What referrals/evaluations should be placed for an individual with Wolf-Hirschhorn?

* Heart defect (cardiology, echocardiogram) * Coloboma, eye anomalies (ophthalmology) * Hearing defect (audiology) * Cleft lip/palate (plastic surgery/ENT) * Seizures (EEG/neurology) * Renal anomalies (Urinalysis, renal ultrasound) * Scoliosis, club foot (orthopedics)

What is the genetic change in Cri Du Chat?

5p-

What are the main features in Cri Du Chat?

* Laryngeal malformation resulting in high pitched monotone cry * Developmental delay/intellectual disability * Craniofacial findings * Other congenital anomalies

What are the medical problems in 5p- (Cri Du Chat)?

Congenital heart disease 35% Abnormal MRI 30% * Absence corpus callosum * Small cerebellum Renal abnormalities 18% * Small kidneys, ectopic Genital abnormalities * Cryptorchidism * Inguinal hernia Developmental delay * Moderate to severe

What percentage of 5p- (Cri Du Chat) are paternal in origin?

80-90%

What percentage of 5p- (Cri Du Chat) are from unbalanced parental translocations?

10% to 15%

What is the genetic cause of Cat-Eye syndrome?

* Isodicentric marker 22q11, resulting in tetrasomy * Note that the marker chromosome regions are proximal to the deletion 22q11.2 critical region

What are the features of Cat-Eye syndrome?

* Coloboma – the “cat eye” * Preauricular anomalies (pits, tags) * Hearing loss * Heart defect * Renal anomaly * Anal atresia * Intellectual disability (mild)