Microdeletion/Duplication Disorders

Question 1

Cri du Chat Syndrome (5p- syndrome)

Answer 1

• 80% of de novo cases are paternal in origin
• Can be due to parental balanced translocation (10-15%)

Critical region: 5p15.2 (cri du chat critical region – correlates to clinical features), 5p15.3 (cat-like cry)

Major features:

• Microcephaly
• Distinct “cat-like” cry
• Severe intellectual disability
• Severe psychomotor developmental delay
• Behavior aggression, hyperactivity
• Repetitive movements
• Cardiac anomalies
• Scoliosis
• Severe malocclusion/Cleft palate
• Coarsening of facial features with age
• Thymic dysplasia
• Inguinal hernia
• Cryptorchidism
• Hypogonadism
• Renal malformations
• GI issues

Question 2

William Syndrome

Answer 2

Chromosome affected: Deletion of 7q11.23
-Contains the ELN (elastin) gene

Major features:

• Cardiovascular disease
• Supravalvular aortic stenosis
• Pulmonic stenosis
• Any valve may be affected by stenosis (absent ELN!!)
• Mild-to-severe intellectual disability
• Strong verbal/language skills, talkative
• Friendly personality, but have high amounts of anxiety
• Distinctive hoarse voice
• Connective tissue anomalies (ABSENT ELN!!!!)
• Endocrine dysfunction
• Stellate iris
• Progressive sensorineural hearing loss
• Coarse facies, with coarsening over time

Question 3

Miller-Dieker Lissencephaly Syndrome (MDLS)

Answer 3

Chromosome affected: Deletion of 17p13.3

Major features:

• Lissencephaly (smooth brain)
• Intellectual disability
• Epilepsy
• Death in infancy or early childhood
• Dysmorphic features

Question 4

22q11.2 Deletion Syndrome (DiGeorge, VeloCardioFacial Syndrome)

Answer 4

Chromosome affected: Deletion of 22q11.2

Major features:
-Cardiac anomalies: Interrupted aortic arch, tetralogy of fallot
-Abnormal facies
-Thymic aplasia: recurrent infection
-Cleft palate
-Hypocalcemia/Hypoparathyroidism
(CATCH 22)

Other features:

• Intellectual disability or learning disabilities
• Growth hormone deficiency
• Skeletal anomalies
• Renal anomalies
• Conductive and sensorineural hearing loss
• Feeding and swallowing problems
• Preauricular tags or pits
• Ophthamologic anomalies
• Increased risk for embryonal tumors

Question 5

Wolf-Hirschhorn Syndrome

Answer 5

Chromosome affected: 4p16.3

Major features:

• “Greek warrior helmet” skull/face
• Preauricular tags
• Growth restriction
• Mild-to-profound Intellectual disability
• Coloboma
• CHDs
• Sleep disturbances
• Seizures
• Cleft lip/palate
• Visceral anomalies – liver problems
• Antibody deficiency
• Hand stereotypies

Question 6

Smith Magenis Syndrome

Answer 6

Chromosome affected: Deletion of 17p11.2
Major features:
-Disrupted sleep patterns
-Inverted circadian rhythm of melatonin
-Behavioral disturbances
-Agression, anxiety, impulsiveness, ADD/ADHD
-Reduced pain sensitivity
-Strabismus
-Ear abnormalities/conductive hearing loss
-Dysmorphic features