CRI-DU-CHAT

SYNDROME
Presenter: Dr. Neethu K Nandan
Moderator: Dr. Sanghamitra Godi
SCHEME
◦ Introduction
◦ Epidemiology
◦ Inheritance
◦ Clinical manifestations
◦ Pathophysiology
◦ Diagnosis
◦ Management
◦ Conclusion
INTRODUCTION
TYPES OF CHROMOSOMAL ABNORMALITIES

numericaL structural

trisomy deletions

monosomy duplications

triploidy inversions

translocations
DISORDERS DUE TO DELETIONS

Cri-du-chat Williams Prader willi

disease syndrome syndrome

Angelman
syndrome
 CRI-DU-CHAT
◦ Genetic syndrome resulting from deletion of
short arm of 5p.
◦ Clinical and cytologic aspects were first
described in Lejeune et al in 1963. (Lejeune’s
disease)
◦ Deletions may vary in size leading to very
variable presentations
◦ Cat like cry being the most consistent finding.
EPIDEMIOLOGY ◦ Rare disease

◦ Incidence -1: 20,000 to 50,000 newborns

◦ Prevalance-1:350 among 6000 mentally

retarded people

◦ No specific ethnic correlation

INHERITANCE
◦ De novo deletion – as an isolated event – in 80%

◦ Some familial translocations – ie balanced translocations in mother leading to unbalanced

translocation in children

◦ Deletion occurs due to break points - where there are large number of repeats in the
region.

◦ What predisposes a specific person to this deletion is not known (inconsistent association
with X-ray exposure in utero, maternal disease – toxemia, hyperemesis etc)
◦ The breakpoints range from p13 to p15.2.
◦ 10-50 Mb deletions
◦ May have interstitial deletions as well
◦ partial aneusomy syndromes may result from PATHOPHYSIOLOG
abnormal gene dosage (haploinsufficiency) Y
involving a large number of contiguous genes.
◦ gene inactivation due to the position effect or
rupture of a very large gene
PATHOPHYSIOLOGY
◦ The human Semaphorin F gene (SEMAF) covers at
least 10% of the specified region.
◦ role in guiding migrating neurons.
◦ human δ-catenin (CTNND2), has also been mapped to
5p15.2
◦ involved in cell motility and is expressed early in
neuronal development.
PATHOPHYSIOLOGY
◦ ADAMTS16, -Belongs to the ADAMTS (a disintegrin and metalloproteinase domain
with thrombospondin motifs) gene family, encoding secreted proteinases.

◦ ICE1- The ICE1 product is one protein component of little elongator complex ELL,
which regulates the transcription of small nuclear RNAs (snRNA)

◦ Telomerase reverse transcriptase (TERT) gene is localized at 5p15.33 and encodes the
rate-limiting component of telomerase complex essential for telomere length
maintenance and sustained cell proliferation. May explain premature aging.
 Clinical features

Physical Medical surgical developmental Behavioral

features problems problems delay manifestation
PHYSICAL APPEARANCE
◦ Micrognathia (96.7%)
◦ Abnormal dermatoglyphics (92%)
◦ Epicanthal folds (90.2%)
◦ Large nasal bridge (87.2%)
◦ Microcephaly and round face (83.5%)
◦ Hypertelorism (81.4%)
◦ Down –turned corners of mouth (81.4%)
◦ Low set ears( 69.8%)
◦ Slanting palpebral fissures( 56.9%)
◦ As the child progresses in to adolescence and
adulthood following features becomes evident

◦ face becomes long and narrow (70.8%),

◦ the supra-orbital arch prominent (31.0%),
◦ the philtrum short (87.8%), the lower lip full
(45.2%),
◦ dental malocclusion (75.0%) ,
◦ palpebral fissures tend to become horizontal
(70.2%),
◦ divergent strabismus (44.7%),
◦ small hands and feet,
◦ premature greying of hair (30.4%)
 PEDIATRIC AGE GROUP
◦ Cat like cry
◦ Developmental delay
◦ Failure to thrive
◦ Asphyxia
◦ cyanotic crises
◦ impaired suction
◦ Hypotonia
◦ Dribbling
◦ infantile spasms-hypsarrhythmia
◦ Recurrent respiratory and intestinal infections
WHY CAT’S CRY?
◦ Unusual cry may be due to structural abnormalities of larynx and pharynx. But
the variability in abnormalities and sometimes normal laryngeal and
pharyngeal structure points towards central origin for the high frequency cry
◦ Narrow larynx
◦ diamond shaped glottis on inspiration.
◦ During phonation the cords approximated anteriorly but left an air space in the
posterior commissure area.
◦ Flaccid aryepiglottic folds
◦ The epiglottis -large and quadrilateral in shape or unusually small
◦ Asymetrical vocal cords
◦ Flaccidity of larynx
 ◦ features of Ehlers-Danlos syndrome
◦ With age, muscle hypotonia is replaced by
hypertonia
MEDICAL ◦ Seizures
COMPLICATIONS ◦ non-ketotic hyperglycinaemia,
◦ Life expectation is good. Mortality
maximum at 1st year of life
 Scoliosis,
flat foot,
pes varus,
inguinal hernia,
SURGICAL diastasis recti,
COMPLICATIONS
Cataract,
congenital luxation of the hip,
Hypospadias,
Cryptorchidism.
DEVELOPMENTAL PROFILE
◦ Developmental delay is very common , but the degree of impairment is
variable.
◦ Fine motor skills are more affected than gross motor skills
◦ 95% manage to walk before age od 8 years
◦ Has ability to communicate, but expression of language is difficult compared
to comprehension. Sign language may help
◦ Usually happy and very sociable children

◦ Hypersensitivity to sensory stimuli

◦ Hyperactivity and inattention
◦ Obsessive attachment to objects BEHAVIORAL
◦ repetitive movements MANIFESTATION
◦ Self injurious behaviour and aggressiveness S
while stressed out
◦ Temper tantrums (such as biting himself, hitting
his head with his hands, head banging)
NEUROIMAGING FINDINGS
◦ Atrophy of the
◦ brainstem mainly involving the pons,
◦ cerebellum,
◦ median cerebellar peduncles
◦ cerebellar white matter
DIAGNOSIS
◦ diagnosis is first of all clinical, based on typical
char- acteristics such as facial dysmorphisms
(facial gestalt), transverse flexion creases,
hypotonia in combination with the peculiar cat-
like cry.
◦ karyotyping
◦ FISH
◦ array CGH and quantitative PCR
MANAGEMENT

◦ Genetic counselling

◦ Pharmacological management

◦ Non pharmacological management

◦ The risk of recurrence is practically negligible for the
cases of a de novo deletion, which are the most
frequent. How- ever, the possibility of gonadal
mosaicism in one of the parents cannot be excluded
GENETIC
◦ some studies showed that the risk of unbalanced COUNSELING?
offspring ranged from 8.7% to 18.8%. The risk for
male and female carriers was similar. Genetic
counselling is useful in them
 ◦ Symptomatic management

PHARMACOLOGICAL ◦ Management for hyperactivity and

MANAGEMENT inattention
◦ Antipsychotics if severe aggressiveness.
◦ Baclofen for hypertonia
 NON PHARMACOLOGICAL
MANAGEMENT

FOR NON BEHAVIORAL FOR BEHAVIORAL

SYMPTOMS SYMPTOMS
 NON BEHAVIORAL
SYMPTOMS
◦ logopedia and physiotherapy for dribbling
◦ Physiotherapy for hypotonia and hypertonia
◦ Dental occlusion correction and hygiene maintenance
◦ High fibre diet for constipation
◦ Manage sleeping difficulties
◦ establishing a routine
◦ Stimulus control
◦ Dark silent room for sleep
◦ speech therapy BEHAVIORAL
◦ Special schools INTERVENTION
◦ Avoid overstimulating S
environments
◦ Social skills-oriented therapy
◦ Sensory processing interventions.
CONCLUSION
◦ Cry-du-chat disease is a rare genetic disorder.
◦ Occurs mostly de novo.
◦ Characteristic findings being - cat like cry, microcephaly, developmental delay
etc.
◦ Variable presentation due to difference in lengths of deletions.
◦ Usually has less mortality after crossing first year of life.
◦ Early interventions lead to better functioning.
◦ Can achieve autonomy.
REFERENCES
◦ Cornish KM, Pigram J. Developmental and behavioural characteristics of cri du chat syndrome. Arch Dis Child. 1996;75(5):448-
450.
◦ Cerruti Mainardi P. Cri du Chat syndrome. Orphanet J Rare Dis. 2006;1:33.
◦ Rodríguez-Caballero A, Torres-Lagares D, Rodríguez-Pérez A, Serrera-Figallo MA, Hernández-Guisado JM, Machuca-Portillo G.
Cri du chat syndrome: a critical review. Med Oral Patol Oral Cir Bucal. 2010;15(3):473-478.
◦ Zhang B, Willing M, Grange DK, et al. Multigenerational autosomal dominant inheritance of 5p chromosomal deletions. Am J
Med Genet A. 2016;170(3):583-593.
◦ Chehimi SN, Zanardo ÉA, Ceroni JRM, et al. Breakpoint delineation in 5p- patients leads to new insights about microcephaly and
the typical high-pitched cry. Mol Genet Genomic Med. 2020;8(2):957-960.
◦ Corcuera-Flores JR, Casttellanos-Cosano L, Torres-Lagares D, Serrera-Figallo MÁ, Rodríguez-Caballero Á, Machuca-Portillo G.
A systematic review of the oral and craniofacial manifestations of cri du chat syndrome. Clin Anat. 2016;29(5):555-560.
◦ Mainardi PC, Pastore G, Castronovo C, et al. The natural history of Cri du Chat Syndrome. A report from the Italian Register. Eur J
Med Genet. 2006;49(5):363-383.
◦ Manning KP. The larynx in the cri du chat syndrome. J Laryngol Otol. 1977;91(10):887-892.
 INTERNATIONAL CRI-DU-CHAT
DISEASE IS CEELBRATED ON 5TH MAY

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