Chromosomal Syndromes: Cri du Chat Syndrome

Chromosomal
Syndromes:
Cri du Chat Syndrome
Chromosomal Syndrome: Cri du Chat
(Karotype)
Cri du Chat syndrome is caused by a deletion of the end of the short arm
of chromosome 5 (written as 5p-). Identified by J Lejeune in 1963 (French
geneticist)
Cri du Chat: Karotype
French term for “cry of the cat” because of the high pitched cry and voice.
Cri du Chat: Phenotype
• 1 of every 50,000 births
• Occurs as a random event
during formation of reproductive
cells or early fetal development.
• Small size at birth
• Microcephaly (including larynx)
• High palate or possible cleft
• Hypertolerism
• Ptosis (epicanthic folds)
• Mental disability (likely severe)
• Chronic otitis media
• Delayed motor development
• Normal life expectancy
Cri du Chat
Cri du Chat:
Phenotype
Cri du Chat: Communication
• Oral speech seldom
develops
• Severe language disorder
• Possible hypernasality
• Possible hearing loss
• Children tend to be loving
& very social
Cri du Chat: Communication
Genetic Syndrome:
Crouzon Syndrome
Photo from M.O. Crouzon's
original publication
Genetic Syndrome: Crouzon
Syndrome (Karotype)
Caused by mutations in a specific gene (FGFR2) located on
Chromosome 10. The gene is associated with growth factors in face
and skull. Identified by Crouzon in 1912 (French neurosurgeon).
Crouzon Syndrome
• Characterized by
abnormalities of skull &
face, and hands & feet.
• There is premature closure
of some of the sutures of
the skull (craniosynostosis)
resulting in an abnormally
shaped head and an
abnormally shaped face
with shallow eye sockets
and under-development of
the midface.
• Technical name is
Craniofacial Dysostosis
Crouzon Syndrome: Phenotype
• Premature fusion of cranial
sutures
• Mid-face hypoplasia (underdeveloped)
• Beak-shaped nose
• Exorbitism (bulging eyes)
• Low-set ears
• Class III malocclusion
• Possible otitis media
• Mental disability is rare
Crouzon Syndrome
•
•
•
•
•
Occurs in 1 out of every 60,000 births
Normal life expectancy
No sex differences
Craniectomy to correct skull abnormalities
Facial reconstruction to correct mid-face
abnormalities
Schematic of procedure to advance the forehead and middle third of the face
Craniofacial Reconstruction
Young woman before and
after surgery to correct
orbital and maxillary
abnormalities
Two-year-old boy before and
after surgery to extend
forehead/brow
Crouzon Syndrome: Post-Operative
Crouzon Syndrome: Post-Op
Crouzon Syndrome: Communication
• Normal onset of speech
and language
• Articulation disorder
resulting from Class III
• Hyponasality due to
small nasal port
• Possible otitis media
leading to hearing loss
Genetic Syndromes:
Foetal Alcohol
Syndrome
"Of all the substances of abuse, including
heroin, cocaine, and marijuana, alcohol
produces by far the most serious
neurobehavioral effects in the fetus.”
--Institute of Medicine 1996 Report to Congress
Fetal Alcohol Syndrome by Anuppa Caleekal (1996)
Some Facts about Alcohol
• Legally intoxicated is defined
as a Blood Alcohol Level
(BAL) of .08%.
• Permanent brain cell
damage begins at a BAL of
.07%.
• A 100 lb (45 kg) female
consuming 5 standard drinks
will reach a BAL of .25% three times the legal limit.
BAL reduces .01% per hour.
• A drink equals a 12 oz. regular
beer, 1.5 oz. shot of 80 proof
liquor, or 4 oz. glass of regular
table wine.
Alcohol as a
Teratogen
• Foolish, drunken, or
harebrain women
most often bring
forth children like
unto themselves
Aristotle in Problemata
(384-322 bc)
FAS: Karotype
• Ethanol (drinking alcohol)
alone is found to interact with
over 1000 genes & cell events.
• Difficult to pinpoint the exact
gene (and how the gene is
mutated) because of issues
related to amount, time of
consumption, and interaction
with other drugs.
A gene array
Effects of Alcohol as a Teratogen on the Baby
• 3 out of 5 women drink alcohol
• Women metabolize alcohol quicker than
men and get intoxicated more easily.
• When women are pregnant (and drink)
the foetus receives a strong dose of
alcohol.
• 3 in 1000 births show full signs of FAS
• 10 in 1000 births show some signs,
called Foetal Alcohol Effects (FAE)
• Type & severity of condition is dependent on when abuse occurred:
Early in pregnancy will affect foetal development of face,
limbs, cardiac & brain development
Late in pregnancy will affect brain (IQ)
FAS: Phenotype
50% or more cases of FAS show:
• Below average height & weight
• Microcephaly
• Micrognathia
• Poor fine & gross motor coordination
• Thin upper lip
• No philtrum
• Short, upturned nose
• Hyperactivity
• Cognitive impairment
• Shortened (and bent) little finger
FAS: Phenotype
FAS: Communication
• General delay in communication
development
• Articulation problems due to poor motor
coordination
• Language delay due to possible intellectual
impairments
• Possible swallowing difficulties
• Possible otitis media