Down Syndrome Vignette

Question 1

Chromosomal abnormalities

Answer 1

Trisomy of chromosome 21, Robertsonian Translocation, Mosaic Down Syndrome

Question 2

Trisomy of chromosome 21

Answer 2

o Three complete copies of chromosome 21 from meiotic nondisjunction
o Meiotic error usually occurs during maternal meiosis I
o 95% of patients

Question 3

Robertson translocation

Answer 3

o Translocation between chromosome 21q and the long arm of another acrocentric chromosome (chromosome 14 or 22) in the maternal germ line
o The carrier mother thus has the karotype 45, XX rob(14;21) (only 45 chromosomes resulting from the union of chromosome 21 with another acrocentric chromosome)
o The affected child has the karotype 46,XY, rob(14;21)+21 - Two copies of the normal chromosome 21 plus the extra translocated copy of 21
o 3% of patients

Question 4

Mosaic Down Syndrome

Answer 4

o Patient has a mixture of the normal and trisomy 21 karotypes
o Milder than typical trisomy 21 with variability based on the proportion of trisomy 21 cells
o Caused by nondisjunction event in early mitotic divisions
o 2% of patients

Question 5

Down Syndrome is typically detected by _______

Answer 5

karotyping

Question 6

Karotyping is most often done by

Answer 6

staining the chromosome of metaphase cells (when the chromatin is condensed) with Giemsa stain, resulting in G-band stains on the chromosomes that can be viewed under a microscope

Question 7

Fluorescence In Situ Hybridization (FISH) allows for _______ associated with Down Syndrome

Answer 7

earlier, more rapid detection of chromosomal abnormalities

Question 8

With FISH,

Answer 8

DNA probes specific for the chromosome or region of chromosome are hybridized to the patients DNA and detected by their fluorescence. In a Down Syndrome patient with trisomy 21, a probe specific for chromosome 21 would reveal the presence of three chromosome 21s.

Question 9

physical features (phenotype) seen in a patient with Down Syndrome

Answer 9

• Hypotonia
• Brachecephaly (flat back of head)
• Dysmorphic facial features
• Heart murmur
• Abnormal genitalia (especially in males)
• Dysmorphic extremities

Question 10

Understand the birth defect problems seen in patients with Down Syndrome

Answer 10

• Heart defects-an atrioventricular canal requiring surgical intervention
• GI abnormalities including atresias and Hirshsprung’s disease

Question 11

Atresia

Answer 11

abnormal closure of esophagus or duodenum

Question 12

Hirshsprung’s disease

Answer 12

bowel obstruction resulting from missing ganglia in colon

Question 13

Understand the problems seen in patients with Down Syndrome presenting later in life

Answer 13

• Midface hypoplasia may lead to frequent ear infections, eye infection from narrowed tear ducts and airway obstruction
• Eye problems-cataracts, myopia, etc.
• Ear problems-hearing loss
• Thyroid disease
• Celiac disease
• Diabetes
• GERD and constipation
• Developmental disabilities and autism (1:10 cases)
• Depression and Alzheimer’s disease

Question 14

Development and behavioral phenotype of a patient with Down Syndrome

Answer 14

Intellectual disability in Down Syndrome patients is typically mild to moderate (av IQ of a pt with Down Syndrome is 50 with a range of 30 to 60.) Those at the upper end of the range may attain 4th to 6th grade reading skills. Persons with down-syndrome can provide for basic self-help needs. Degrees of intellectual and social skills can vary greatly among patients. Down syndrome patients require specialized education and assistance with more complex daily activities.
-inc risk of Autism and Alzheimers

Question 15

Dysmorphic facial features:

Answer 15

mid-face hypoplasia, up-slanting palpebral fissures, epicanthal folds (skin fold of upper eyelid), Brushfield spots (brown spots of the iris), small pinnae with folded appearance, flat nasal bridge

Question 16

Dysmorphic extremities:

Answer 16

single transverse palmer crease, incurving pinky, small digits, increased space between 1st and 2nd toes, increased joint range of motion