10/15 - Segmental Aneusomy & Contiguous Gene Syndromes

Question 1

Developmental delay

Answer 1

• minimal physical findings
• normal physical exam
• 5%-25% of children have genetic causes

Question 2

MR - Intellectual delay

Answer 2

• IQ <70

- Degree of mental retardation and measured IQ and expected mental age as an adult in years

Question 3

DiGeorge/VCF

Answer 3

• Deletion 22q.11
• Conotruncal heart defects
• Learning disabilities
• Psychiatric
• Speech/Language
• Dysmorphism

Question 4

CMT1 Clinical Presentation

Answer 4

• Demyelinating peripheral neuropathy
• Foot deformities including pes cavus, hammer toes and foot drop
• Hyporeflexia/areflexia
• Claw hand deformities (in severe cases)

Question 5

Newer chromosome tests

Answer 5

• microarrays genomic
• microarrays protein CHIP
• genome-wide array: CGH

Question 6

Wolf-Hirschorn

Answer 6

• Deletion 4p
• 1/50,000
• 90% de novo
• Deletion of short arm chromosome 4 involving 4p16.3 to pter
• Critical region mapped to 4p16.3
• Some microdeletions seen only by FISH
• Death in infancy common can survive to adulthood
• “Greek warrior helmet”

Question 7

Clinical characteristics of Wolf-Hirschorn

Answer 7

• IUGR with microcephaly
• Wideset eyes with “Greek warrior helmet” nasal bridge
• Colobomas
• Cleft lip/palate, fish-like mouth
• Midline scalp defects
• CHD, renal, and genital malformations
• Club feet
• Failure to thrive
• Profound MR and seizures

Question 8

Cru Du Chat

Answer 8

• Deletion 5p
• One of the mot common human chromosome deletion syndromes
• 1/20,000 to 1/50,000 live births
• 85% de novo deletion - paternal origin 80%
• Remaining cases due to parental translocation involving 5p
• Patients noted to have mew-like cry (abnormal laryngeal development)

Question 9

Clinical features of Cru Du Chat

Answer 9

• Microcephaly
• Round Face
• Hypertelorism
• Broad nasal bridge
• Low-set ears
• Down-slanting palpebral fissures
• Cardiac defects

Question 10

Gene regions for Cru DU Chat

Answer 10

• Size of deletion may correlate with severity of phenotype
• Critical region for mew-like cry is 5p15.3
• Remaining clinical features mapped to 5p15.3
• Clinical features are less obvious with age
• Mental retardation less severe than previously thought

Question 11

CGH+SNP Microarray

Answer 11

• Known/suspected consanguinity ~5% of families in USA
• Ancestral relatedness
• Families from Middle East, North Africa, and West Asia
• Isolated communities (Amish)
• Known/suspected incest
• Patients with recessive disorder - metabolic, rare syndromes
• Suspected imprinting disorder