Trisomies and Microdups/dels Flashcards
What is the most common chromosomal aneuploidy occurring in humans? Most frequently occurring live-born aneuploidy?
T21
Describe the reason for the features seen in DS
Down syndrome critical regions are a few chromosomal regions associated with partial trisomy for a gene called Has21. The DSCR on 21q21.22 is responsible for many clinical features of DS.
What cardiac features are present in individuals with T21
Most common and leading cause associated with morbidity and mortality in pts, especially in the first 2yrs of life
CHDs in up to 50% of babies
most common: AVSD which is associated with mutations in CRELD1 then VSD
What can cause DS?
AMA
Sporadic trisomy (95%)
isochromosome: 2 long arms separate together instead of the long and short arms while in Robertsonian t (2-4% of pts; mostly 14;21)
1% caused by mosaicism
What percent of T21 fetuses are lost before term? What influences the chances of having a fetus with T21? Why is it the most common viable live chromosomal aneuploidy
50-75%
AMA
small number of genes on chromosome 21 (Hsa21) which is the smallest and least dense of the autosomes
What percent of babies with T21 have u/s findings? What would these findings be?
50%
Increased NT, absent nasal bone, cardiac anomalies (50%), echogenic bowel, EIF
What percentage of cases of T21 are attributed to mothers over 35? Under 35?
10%; 90%
under 35 is higher bc they have higher birth rates
What is the overall prevalence of T21? Risk at 35 to have a child with T21? at 40? at 45? at 50?
Overall: 1 in 800
at 35: 1 in 300
at 40: 1 in 100
at 45: 1 in 20
at 50: 1 in 5
What are the chances of having a child with T21 if mom is a carrier of Robertsonian t? If dad is?
15% if mom
1% if dad
How would a 21;21 translocation in a patient with T21 have occurred? If someone were to be a carrier of this translocation, what are the chances their children would have T21
de novo
100% of that person’s children would have T21
What is the most common Robertsonian translocation causing T21
14;21
What gastrointestinal features are present in individuals with T21
duodenal and small bowel stenosis and atresia
annular pancreas
imperforate anus
Hirschsprung disease (neural cells fail to migrate causing a segment of the rectum not being able to have normal peristalsis resulting in failure of normal defecation)
strong association with celiac disease
What hematologic features are present in individuals with T21
neutrophilia, thrombocytopenia, polycythemia (usually mild and will resolve in the first few weeks of life)
transient abnormal myelopoiesis/leukemia: detected during the first wk but resolved by 3mo; can also cause SAB
10x risk of developing leukemia
What neurologic features are present in individuals with T21
reduced brain volume, hypotonia, joint laxity, prone to decreased bone mass, increased risk of fractures, seizures (usually infantile spasms, tonic-clonic, myoclonic)
dementia in pts older than 45yo; 50-75% have dementia by 60yo
What endocrinological features are present in individuals with T21
hypothyroidism which can be congenital or acquired at any time during life
delayed puberty (primary hypogonadism)
What ocular and ENT features are present in individuals with T21
cataracts/iris anomalies/strabismus
anatomical structure of the ear predisposes pts to hearing deficits –> usually conductive hearing loss which is tx with pressure equalization tubes
What diagnostic tests can detect T21 and how
FISH: interphase nuclei most commonly used by using Hsa21 specific probes or the whole of Hsa21
karyotype: 3 Chrom 21’s
What referrals should you make for a pt with T21
Hearing and vision assessment
Thyroid function tests annually
Cardiac referral within first 6mo of life to correct CHDs
developmental pediatrician
pediatric pulmonologist
gastroenterologist
neurologist/neurosurgeon
orthopedic specialist
child psychiatrist
PT/OT/Speech
audiologist
What are the three potential etiologies for T18
Complete T18 (94%): nondisjunction during Me II, most often of maternal origin
Mosaic T18 (less than 5%)
Partial T18 (~2%): only a partial segment of 18q is present in triplicate, results from a balanced translocation or inversion carrier (18p trisomy DOES NOT result in T18 phenotype)
What is the recurrence risk for complete and partial T18
Complete: 0.5-1%
Partial: could be up to 20% depending on translocation
What is the average prevalence of T18? In which sex is it most present in?
1 in 2500
more often in females (3:2 ratio)
fetal loss is higher in males
Describe some of the neurologic and craniofacial findings in T18
Neuro: Neonatal hypotonia followed by hypertonia, Apnea
Seizures, Poor sucking, Delayed psychomotor development and ID
Craniofacial: Skull: Microcephaly, bitemporal narrowing, and prominent occiput.
Face: Triangular and asymmetric face with facial paralysis
Eyes: Microphthalmia, hypertelorism, epicanthus, short palpebral fissures, coloboma of iris, cataract, corneal clouding, hypoplastic supraorbital ridge, upward or downward slanting palpebral fissures, and abnormal retinal pigmentation.
Nose: Prominent nasal bridge with hypoplastic nasal root, upturned nares, and choanal atresia.
Oral cavity: Micro-retrognathia, microstomia, narrow arched palate, cleft lip, and cleft palate.
Ears: Microtia, preauricular appendages, low-set or retroverted ears, and dysplastic ears.
Describe some of the skeletal and cardiovascular features in T18
Severe growth retardation, Short neck, Short sternum, Broad chest, with or without widely spaced small nipples. Incomplete ossification of the clavicle, Hemivertebrae or fused vertebrae, scoliosis, Pectus excavatum , Narrow pelvis and limitation of the hip abduction, Hip dislocation, Arthrogryposis, Clenched hands with overriding fingers, camptodactyly, syndactyly, single palmar crease and clinodactyly of the fifth fingers, radial or thumb hypoplasia, and hypoplastic nails, Rocker-bottom feet with the prominent calcaneus, talipes equinovarus, dorsiflexed great toes
Cardiac defects are found in 90% of Edwards syndrome patients.
Ventricular or atrial septal defect, Patent ductus arteriosus, tetralogy of Fallot, overriding of the aorta, coarctation of the aorta, and hypoplastic left heart syndrome
Polyvalvular heart disease (involving two or more valves; the most common aortic and pulmonary valve
Describe some of the pulmonary and GI issues in pts with T18
Pulmonary hypoplasia, Tracheobronchomalacia, laryngomalacia, Obstructive and central apnea, Early-onset pulmonary hypertension
Omphalocele, Esophageal atresia with Tracheoesophageal fistula , Pyloric stenosis, Ileal atresia, Malrotation, Meckel diverticulum, Diastasis recti , Umbilical hernia