Cri-Du-Chat Syndrome Research Paper

CRI DU CHAT
SYNDROME

WHO DISCOVERED CRI DU
CHAT SYNDROME?
In 1963, JEROME LEJEUNE described a syndrome consisting of multiple congenital anomalies, mental retardation, microcephaly, abnormal face, and a mewing cry in infants with a deletion of a B group chromosome
(Bp-), later identified as 5p-

WHAT IS CRI DU CHAT
SYNDROME?
Cri-du-chat syndrome is an autosomal deletion syndrome caused by a partial deletion of chromosome 5p and is characterized by a distinctive, high-pitched, catlike cry in infancy with growth failure, microcephaly, facial abnormalities, and mental retardation throughout life.

WHAT CAUSES CRI DU
CHAT?
From a review of 331 published cases, estimated that most cri-duchat syndrome cases are the result of de novo deletions
(about 80%), some derive from a familial rearrangement
(12%), and only a few show other rare cytogenetic aberrations, such as mosaicism (3%), rings (2.4%), and de

The deleted chromosome 5 is paternal in origin in about 80% of cases.
Loss of a small region in band 5p15.2 (cridu-chat critical region) correlates with all clinical features of the syndrome except for the catlike cry, which maps to band 5p15.3
(catlike critical region). The results suggest that 2 noncontiguous critical regions contain genes involved in this condition's etiology. EPIDEMIOLOGY
With contemporary

MORTALITY/MORBIDITY

UNITED STATES

interventions, the chance of survival to adulthood is possible.

The estimated prevalence is about 1 in
50,000 live births.

Currently, the mortality rate of cri-du-chat syndrome is 6-8% in the overall population.

The prevalence among individuals with mental retardation is about 1.5 in 1000.

Pneumonia, aspiration pneumonia, congenital heart defects, and respiratory distress syndrome are the most common causes of death. RACE
No racial predilection has been found. SEX
A
significant female predominance is observed in affected newborns, with a maleto-female ratio of 0.72:1.
AGE
The condition is detected in newborns and infants because of the catlike cry and WHAT ARE THE
MANIFESTATIONS?
Newborns have a characteristic mewing cry, a high-pitched monochromatic cry that is considered pathognomonic for this syndrome.
Neonatal
complications include poor sucking, need for incubator care, respiratory distress, Epicanthic Fold
Upward Slanting
Eyes
Flat Nasal Bridge
Protruding
Tongue
Simian Crease
Microcephaly

LATE CHILDHOOD AND
ADOLESCENCE
Affected females reach puberty, develop secondary sex characteristics, and menstruate at the usual time.
The genital tract is usually normal in females, except for a report of a bicornuate

In males, the testes are often small, but spermatogenesis is thought to be normal. HOW IS IT DIAGNOSED?
FLUORESCENCE IN SITU HYBRIDIZATION
(FISH)
Molecular cytogenetic studies using FISH allow the diagnosis to be made in patients with very small deletions. FISH uses genetic markers that have been precisely localized to the area of interest.
The absence of a fluorescent signal from either the maternal or paternal chromosome 5p regions indicates monosomy for that chromosomal region.

CHROMOSOME
COMPARATIVE
GENOMIC
HYBRIDIZATION (CGH)
Chromosome CGH is capable of screening the entire genome for
DNA copy-number alterations in a single hybridization.
The resolution is limited to approximately 5-10 Mb.
The results cannot be directly mapped onto the genome sequence. SKELETAL
RADIOGRAPHY
oMicrocephaly, retromicrognathia oCranial base malformations
(reduced cranial base angle and malformed sella turcica and clivus) oDisproportionately short third, fourth, and fifth
metacarpals and disproportionately long second, third, fourth, and fifth proximal phalanges (common)

MRI oAtrophy of the brainstem, atrophic middle cerebellar peduncles and cerebellar white matter oPossible hypoplasia of cerebellar vermis with enlargement of the cisterna magna and fourth ventricle

ECHOCARDIOGRAPHY
Used to rule out structural cardiac malformations

HOW IS IT TREATED?
Care is supportive. No treatment is available for cri-du-chat syndrome.
Chronic medical problems such as upper respiratory tract infections, otitis media, and severe constipation require appropriate treatment.
Use the relatively good receptive skills to encourage language and

Early stimulation and introduction to sign language are effective means of developing communication skills (50% of children are able to use sign language to communicate).
Behavior modification programs may be successful in managing hyperactivity, short attention span, low threshold for frustration, and self-stimulatory behaviors
(eg, head-banging, hand-waving).
Visual-motor
coordination computerized training improves the visuospatial performance in a child affected by cri-du-chat syndrome

PROGNOSIS
After the first years of life, the mortality
(10%) and morbidity rates are low. About
75% of deaths occurred during the first months of life, and as many as 90% occurred within the first year.
Recent improvements in management and rehabilitation programs have resulted in increased psychomotor development, improved autonomy, and better social adaptation.

Until recently, little was known about the cognitive function of patients with cri-du-chat syndrome. Recent literature indicates that many children can develop some language and motor skills. These children attain the developmental and social skills commonly observed in children aged 5-6 years, although their linguistic abilities are seldom as advanced. Older, home-reared children are usually ambulatory, able to communicate verbally or through gestural sign language, and independent in self-care skills.

THANK YOU!