M3a. Duplication Syndromes

What chromosome duplication is associated with Beckwith Wiedemann syndrome?

Partial duplication of 11p15.5

• aka congenital overgrowth syndrome

What is an associated risk with BWS?

More likely to develop cancer or embryonal tumors

• currently treatment is limited to surgery to correct abnormalities

What are the clinical manifestations of BWS?

• Triad of omphalocele, macroglossia and macrosomatia, and visceromegaly plus

• Umbilical hernia

• Hemihypertrophy

• Gigantism

• Hypoglycemia

• Ear creases/pits

The imprinted gene cluster at 11p15.5 contains at least ___ genes.

3 total

• IGF-2

• H19

• P57kip2 (CDKN1C)

What is IGF-2?

Insulin-like Growth Factor 2

• promotes embryonic growth

• PATERNAL expression only

  • most tissues-biallelic in adult liver

What is H19?

• Tumor suppressor RNA

• MATERNAL expression only

What is P57kip2 (CDKN1C)?

Product (KIP2) or Cyclin-Dependent Kinase Inhibitor 1C

• a growth inhibitor

• MATERNAL expression (leaky paternal expression)

What chromosome duplication is associated with Cat-Eye syndrome?

aka Schmid-Fraccaro Syndrome, a very rare malformation involving chromosome 22 where the p arm and a small section of q arm are tri/tetra-somic instead of 2x

What are the possible chromosomal abnormalities associated with Cat-Eye syndrome?

• 22pter-22q11

  • Partial trisomy

  • Partial tetrasomy

• 22qter-22q11

  • Inverted duplication

What is the cause of the duplication in Cat-Eye syndrome?

• Usually arises spontaneously (de novo)

• Can occur due to unbalanced gamete formation in balanced translocation carriers

What are some clinical manifestations of Cat-Eye syndrome?

• Iris/Optic disc coloboma

• Anal atresia

• Palpebral fissures

• Pre-auricular pits/tags

• Micrognathia

• Hernias

• Cleft palate

• Mild-moderate retardation

What are some associated risks with Cat-Eye syndrome?

Eyes: photophobia, myopia, astigmatism, risk of glaucoma and detached retina

Cardiac defects

Kidney: Missing, extra, or underdeveloped

Skeletal: scoliosis

What is ESAC?

Extra Structurally Abnormal Chromosome

• A marker chromosome where its origin is unidentified

• The effect is dependent on which chromosome and the size

• Frequently in mosaic conditions

When is urgent parental chromosome analysis required for ESAC?

Familial (39% cases): 0% phenotypic abnormality

De novo (61% cases): usually low risk

• Exception: proximal 15q is high risk

Abnormal 3:1 segregation (rare): high risk serious phenotypic abnormalities certain

What FISH probes are used for ESAC?

Chromosome 15 and 22 most common

• Pericentric/satellite regions

• Pericentromeric duplicons may facilitate unequal crossing over