Constitutional Abnormalities And Clinical Indications - Structural And Microdeletion Syndromes

Front 1

Wolf-Hirschhorn Syndrome

Back 1

- Deletion 4p16.3

Mechanism
- deletion, terminal; unbalanced translocation

Front 2

Wolf-Hirschhorn Syndrome
Clinical Features

Back 2

- Severe growth retardation (IUGR)
- Severe MR
- MIcrocephaly (small head, abnormal brain development)
- Hypotonia
- Cleft lip/palate
- Wide-set eyes, broad nose
- Heart defect
- "Greek Warrior Helmet" (or Magneto helmet)

Front 3

Cri-du-Chat Syndrome

Back 3

- Deletion 5p15.2

Mechanism
- Deletion, terminal, unbalanced translocation

Front 4

Cri-du-Chat Syndrome
Clinical Features

Back 4

- Cat-like cry in infancy
- Mental retardation
- Language difficulty
- Poor muscle tone
- Congenital heart defect (CHD(
- Normal life expectancy
- Happy and interactive

Front 5

WAGR Syndrome

Back 5

- Aniridia-Wilms Tumor Association
- Deletion 11p13

Mechanism
- de novo: interstitial deletion, possibly inherited insertion/deletion

Front 6

WAGR Syndrome
Clinical Features

Back 6

- Wilms tumor: kidney tumor of childhood (50%) of patients
- Aniridia: absence of the iris of the eye
- Genital/Urinary Abnormalities (hypospadia, cryptorchidism)
- Retardation (mental): mild to severe

Front 7

Pallister-Killian Syndrome

Back 7

- Mosaic tetrasomy 12p [+i(12)(p10)]

Mechanism
- Mosaic tetrasomy 12p [isochromosome formation]

Front 8

Pallister-Killian Syndrome
Clinical Features

Back 8

- Hypotonia
- Facial abnormalities (high forehead, broad nasal bridge, wide spaced eyes, low-set ears, broad nose, cupids bow lip, rounded cheeks, wide mouth with a thin upper lip and a large tongue)
- Sparse scalp hair at birth
- Hypopigmentation, streaks of uneven pigmentation
- Mental retardation

Front 9

Pallister-Killian Syndrome
Cell Culture

Back 9

- found in mosaic form
- found in skin fibroblasts
- found in fibroblasts
- usually NOT found in PB analysis (ab cells cycle out over time)
- an isochromosome 12p looks like an isochromosome 21

Front 10

Miller-Dieker

Back 10

- Deletion 17p13.3 (terminal)

Mechanism
- de novo: 50% have a microscopically visible deletion and the remainder has a submicroscopic deletion; chromosome rearrangement

Front 11

Miller-Dieker
Clinical Features

Back 11

- Lissencephaly: brain is incomplete, 4 layers, not 6, smooth surface
- Ridges in center of forehead especially when crying
- Microcephaly (small head)
- Prominent forehead
- Severe mental retardation
- Short nose and anteverted nostrils
- Feeding and breathing problems
- Usually only live a short time

Front 12

Smith-Magenis

Back 12

- Deletion 17p11.2

Mechanism
- Deletion, interstitial

Front 13

Smith-Magenis
Clinical Features

Back 13

- Brachycephaly (flat head)
- Square shaped face with deep set eyes, prominent lower jaw, pognathism, broad nasal bridge, hoarse voice
- Hypotonia
- Feeding problems
- Reversed circadian rhythms (awake at night, sleeps during the day)
- Behavioral problems: self injury-biting, nail and skin picking; repetitive self hugging; tantrums

Front 14

Cat Eye Syndrome

Back 14

- Duplication 22q11.1

Mechanism
- tetrasomy or trisomy, sometimes mosaic, frequently bisatellited dicentric marker

Front 15

Cat Eye Syndrome
Clinical Features

Back 15

- Coloboma of iris
- Downslanting palpebral fissures
- Anal atresia
- Cardiac defects
- Normal to mild mental retardation
- Seizures

Front 16

Velo-Cardio-Facial Syndrome (VCF)

Back 16

- Deletion 22q11.2

Mechanism
- Deletion, interstitial; microdeletion; unbalanced translocation

Front 17

Velo-Cardio-Facial Syndrome (VCF)
Clinical Features

Back 17

- Cleft lip/palate
- Long face, smooth philtrum, long prominent nose with bulbous tip
- Heart abnormalities including VSD (ventricular spetal defect)
- Learning disabilities
- Genitourinary anomalies
- Hypernasal speech
- Slender hands and fingers
- Mild to severe learning disorders
- Immunologic dysfunction due to absent/hypoplastic thymus (affects T-cell development resulting in frequent infections), these patients have true DiGeorge syndrome

Front 18

DiGeorge Syndrome

Back 18

- DiGeorge anomaly or DiGeorg Sequence (deletion 22q11.21-11.23)

Mechanism
- Deletion, interstitial; microdeletion; unbalanced translocation

Front 19

DiGeorge Syndrome
Clinical Features

Back 19

- Thymus hypoplasia or aplasia resulting in deficit in cellular immunity; T-cells diminished and don't respond to PHA Hypoparathyroidism
- Abnormalities of the aortic arch and othe cardiac anomalies
- Dysmorphic features are subtle, including (hypertelorism; downslanting eyes, notched/low-set ears, micrognathia - small jaw: can interfere with feeding, cleft lip/palate, hypocalcemia - low blood calcium levels)

Front 20

Williams-Buerens Syndrome

Back 20

- deletion 7q11.23

Mechanism
- Interstitial deletion - elastin (ELN) and the LIM-kinase I (LIMK1) genes are located in the critical region

Front 21

Williams-Buerens Syndrome
Clinical Features

Back 21

- Mental deficiency/developmental delay; IQ = 40-100
- Congenital heart defects (supravalvular aortic stenosis)
- Broad brow, short upturned nose, full cheeks
- Full lips and wide mouth, long philtrum
- Stellate pattern to iris
- Hoarse voice, premature aging
- Congenial personality (very social, talented)
- Hypercalcemia

Front 22

Langer-Giedion Syndrome

Back 22

- deletion 8q24.11-24.13 (Tricho-Rhino-Phalangeal Syndrome type 111, TRPII)

Mechanism
- Interstitial or terminal deletion (extremely rare)

Front 23

Langer-Giedion Syndrome
Clinical Feaures

Back 23

- Mental retardation
- Fine, sparse scalp hair; large bulbous nose
- Long, simple philtrum, thin upper lip
- Large, laterally protruding ears
- Loose, redundant skin in infancy that regresses with age
- Exostoses of long bones: bone spurs or lumps
- Epiphyseal coning [growth at the end of the bone]: tendency toward bone fracture

Front 24

Prader-Willi Syndrome

Back 24

- paternal deletion 15q12

Mechanism
- deletion of paternal locus, absence or inactivation of paternal 15q12 (maternal UPD and/or mutation)

Front 25

Prader-Willi Syndrome
Clinical Features

Back 25

- Learning difficulties, IQ = 70
- Hypotonia causing early eating problems
- Small hands and feet
- Hypogonadism: incomplete sexual development
- Chronic feeling of hunger: compulsive eating disorder and obesity

Front 26

Angelman Syndrome

Back 26

- maternal deletion 15q12

Mechanism
- deletion of maternal locus, absence or inactivation of maternal 15q12 (paternal UPD and/or mutation)

Front 27

Angelman Syndrome
Clinical Features

Back 27

- Severe MR, no language development
- Happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements "marionette-like" gait ("Happy Puppet Syndrome")
- Microcephaly

Front 28

Rubinstein-Taybi

Back 28

del(16)(p13.3)

Front 29

Alagille Syndrome

Back 29

del(20)(p11.23)

Front 30

Retinoblastoma-Eye Tumor

Back 30

del(13)(q14)

Front 31

Charcot-Marie-Tooth (CMT)

Back 31

dup(17)(p12)

Front 32

SRY Deletion

Back 32

del(Y)(p11.3)
(phenotypically a female, deletion where makes a male, a male)

Front 33

Azoospermia

Back 33

del(Y)(q11.2)