Chromosomal Disorders Flashcards
What are the major anomalies in the newborn stage of Trisomy 21?
- Heart defect
- Duodenal atresia
- Hirschsprung Disease
What labs are abnormal in the newborn stage of Trisomy 21?
- Transient myelopoiesis
- (20-30% risk leukemia)
- Hypothyroidism
What are the heart anomalies in Trisomy 21?
Heart (50%)
* AV Canal (AVSD) (40%)
* VSD (32%)
* ASD (10%)
* Tetralogy of Fallot (6%)
25-40% of children with duodenal atresia have what disorder?
Trisomy 21
12% of patients with Hirschprung have what disorder?
Trisomy 21
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
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)
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%.
What is the incidence of Trisomy 21 in a 35 year-old pregnant person?
1 in 350
What is the incidence of Trisomy 21 in a 40 year-old pregnant person?
1 in 100
What percentage of nondisjunction occurs in meiosis I in Trisomy 21? Meisois II?
77% meiosis I, 23% meiosis II
What percentage of Trisomy 21 is due to a Robertsonian translocation?
4%
What percentage of Trisomy 21 is mosaic?
1%
What is the recurrence rate of T21 with a Robertsonian translocation?
Empirically derived
* t(14:21) 10-15% mother, <5% father
What is the recurrence risk of 21q21q isochromosome?
100%
Is T18 due to nondisjunction in Meiosis I or II?
majority Meiosis II
What percentage of T18 are mosaic?
5%
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)
