Microdeletion and Microduplication syndromes

Question 1

Monosomy 1p36 (1p36 deletion syndrome)
 Syndrome features:

Answer 1

oMild to severe intellectual disability
oDevelopmental delay
oLimited or absent speech
oAggression, self-injurious behavior
oAutistic behaviors
oDysphagia
oHypothyroidism
oHyperreflexia
oMicrocephaly
oHypotonia
oScoliosis/kyphosis
oBrain MRI abnormalities:
oVisual problems:
oHeart defects
oIncreased risk for neoplasia:
oDysmorphic features

Question 2

Monosomy 1p36

Features: Visual problems and Heart defects

Answer 2

oVisual problems:
	Cataracts
	Nystagmus
	Strabismus
	Hypermetropia
oHeart defects
	Infantile dilated cardiomyopathy
	Patent ductus arteriosus 
	Tetralogy of Fallot

Question 3

Monosomy 1p36

Features: Neoplasms and Dysmorphic features

Answer 3

o Increased risk for neoplasia:
	Non-Hodgkin’s lymphoma
	Lung cancer
	Prostate cancer
	Colorectal cancer
	Breast cancer
	Ovarian cancer
	Melanoma
	Neuroblastoma
	Cervical cancer
	Hepatoma

o Dysmorphic features:
 	Frontal bossing
	Small, pointed chin
	Flat nose
	Deep-set eyes
	Thickened helices
	Slanting palpebral fissures
	Midface hypoplasia
	Orofacial clefting

Question 4

Wolf-Hirschhorn Syndrome: Chromosome?

Answer 4

Chromosome affected: 4p16.3

Question 5

Wolf-Hirschhorn Syndrome

Answer 5

Major features:
•“Greek warrior helmet” skull/face
      oMicrocephaly, ocular hypertelorism
•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

Cri Du Chat Syndrome: Genetics

Answer 6

Inheritance: Autosomal dominant
•Typically de novo (85-90%)
•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)

Question 7

Cri Du Chat Syndrome: Major Features

Answer 7

•Microcephaly
•Distinct “cat-like” cry
•Severe intellectual disability
•Severe psychomotor developmental delay
•Behavior aggression, hyperactivity
•Repetitive movements
•Excessive drooling
•Cardiac anomalies
•Scoliosis
•Severe malocclusion
•Coarsening of facial features with age
•Dysmorphic features:
    oBroad nasal bridge
    oEpicanthal folds
    oDown-slanting palpebral fissures
    oMicrognathia
    oHypertelorism
    oStrabismus
    oBrachydactyly
    oSingle palmar creases

Question 8

Cri Du Chat Syndrome: Minor Features

Answer 8

•Thymic dysplasia
•Inguinal hernia
•Cleft palate
•Cryptorchidism
•Hypogonadism
•Renal malformations
•Club foot
•GI issues
   oMegacolon
   oIntestinal malrotation

Question 9

Williams Syndrome (Williams-Beuren Syndrome)

Answer 9

Inheritance: Autosomal dominant
• Typically de novo
Chromosome affected: Deletion of 7q11.23
• Contains the ELN (elastin) gene

Question 10

Williams Syndrome (Williams-Beuren Syndrome)
  Major Features

Answer 10

•Cardiovascular disease
   oSupravalvular aortic stenosis
   oPulmonic stenosis
   oAny valve may be affected by stenosis (absent ELN!!)
•Distinctive hoarse voice
•Connective tissue anomalies (ABSENT ELN!!!!)
    oInguinal/umbilical hernia
    oRectal prolapse
    oJoint limitation or laxity
    oSoft, lax skin
•Mild-to-severe intellectual disability
•Strong verbal/language skills
     oPoor visuospatial construction
•Characteristic personality
   oFriendly
   oTalkative
   oEmpathetic
   oAnxiety problems
•Endocrine dysfunction
    oHypothyroidism
    oHypercalciuria/Hypercalcemia
    oDiabetes mellitus
•Stellate iris
•Progressive sensorineural hearing loss
•Coarse facies, with coarsening over time
   oBitemporal narrowing
   oBroad forehead
   oStrabismus
   oMicrognathia
   oMalocclusion
   oEpicanthal folds
   oPeriorbital puffiness

Question 11

Smith-Magenis Syndrome: Chromosome?

Answer 11

Chromosome affected: Deletion of 17p11.2

Question 12

Smith-Magenis Syndrome Major Features

Answer 12

•Disrupted sleep patterns
oInverted circadian rhythm of melatonin
•Behavioral disturbances
oAgression, anxiety, impulsiveness, ADD/ADHD
•Reduced pain sensitivity
•Strabismus
•Ear abnormalities/conductive hearing loss
•Dysmorphic features

Question 13

Miller-Dieker lissencephaly syndrome (MDLS): Genetics

Answer 13

Inheritance: Autosomal dominant

Chromosome affected: Deletion of 17p13.3

Question 14

Miller-Dieker lissencephaly syndrome (MDLS) Major features

Answer 14

•Lissencephaly (smooth brain)
•Intellectual disability
•Epilepsy
•Death in infancy or early childhood
•Dysmorphic features:
   oUpturned nares
   oThickened upper lip
   oFrontal bossing
   oSmall jaw
   oLow-set, posteriorly rotated ears
o	Midface hypoplasia
o	Hypertelorism

Question 15

DiGeorge Syndrome (22q11.2 deletion syndrome)

Answer 15

Inheritance: Autosomal dominant
Chromosome affected: Deletion of 22q11.2
Major features:
•Cardiac anomalies
oInterrupted aortic arch, Tetralogy of Fallot
•Abnormal facies
•Thymic aplasia
oRecurrent infection
•Cleft palate
•Hypocalcemia/Hypoparathyroidism

Question 16

DiGeorge Syndrome: Other features:

Answer 16

• 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