Cri du chat
Encyclopedia
Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p minus syndrome or Lejeune’s syndrome, is a rare genetic disorder due to a missing part of chromosome 5. Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry
of affected children. It was first described by Jérôme Lejeune
in 1963. The condition affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio.
Other common findings include hypotonia
, microcephaly
, growth retardation, a round face with full cheeks, hypertelorism
, epicanthal folds, down-slanting palpebral fissure
s, strabismus
, flat nasal bridge, down-turned mouth, micrognathia, low-set ears, short fingers, single palmar creases, and cardiac defects (e.g., ventricular septal defect
[VSD], atrial septal defect
[ASD], patent ductus arteriosus
[PDA], tetralogy of Fallot
). People with Cri du chat are fertile and can reproduce.
Less frequently encountered findings include cleft lip and palate, preauricular tags and fistulas, thymic dysplasia, intestinal malrotation
, megacolon
, inguinal hernia
, dislocated hips, cryptorchidism
, hypospadias
, rare renal malformations (e.g., horseshoe kidneys, renal ectopia
or agenesis, hydronephrosis
), clinodactyly
of the fifth fingers, talipes equinovarus, pes planus, syndactyly
of the second and third fingers and toes, oligosyndactyly, and hyperextensible joints. The syndrome may also include various dermatoglyphics, including transverse flexion creases, distal axial triradius, increased whorls and arches on digits, and a single palmar crease.
Late childhood and adolescence findings include significant intellectual disability, microcephaly
, coarsening of facial features, prominent supraorbital ridges, deep-set eyes, hypoplastic nasal bridge, severe malocclusion
, and scoliosis
.
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 uterus
. In males, testes are often small, but spermatogenesis is thought to be normal.
number 5, also called "5p monosomy". Approximately 90% of cases results from a sporadic, or randomly-occurring, de novo deletion. The remaining 10-15% are due to unequal segregation of a parental balanced translocation where the 5p monosomy is often accompanied by a trisomic portion of the genome. These individuals may have more severe disease than those with isolated monosomy of 5p.
Most cases involve total loss of the most distant 20-10% of the material on the short arm. Fewer than 10% of cases have other rare cytogenetic aberrations (e.g., interstitial deletions, mosaicisms, rings and de novo translocations). The deleted chromosome 5 is paternal in origin in about 80% of de novo cases.
Loss of a small region in band 5p15.2 (cri du chat critical region) correlates with all the clinical features of the syndrome with the exception of 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. Two genes in these regions, Semaphorine F (SEMA5A) and delta catenin
(CTNND2), are potentially involved in cerebral development. The deletion of the telomerase reverse transcriptase
(hTERT) gene localized in 5p15.33 may contribute to the phenotypic changes in cri du chat syndrome as well.
and genetic testing
may be offered to families with individuals who have cri du chat syndrome. Prenatally the deletion of the Cri du chat related region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi samples with BACs-on-Beads technology. Children may be treated by speech, sound, and occupational therapists. Cardiac abnormalities often require surgical correction.
Crying
Crying is shedding tears as a response to an emotional state in humans. The act of crying has been defined as "a complex secretomotor phenomenon characterized by the shedding of tears from the lacrimal apparatus, without any irritation of the ocular structures"...
of affected children. It was first described by Jérôme Lejeune
Jérôme Lejeune
Servant of God Jérôme Jean Louis Marie Lejeune was a French Catholic pro-life paediatrician and geneticist, best known for his discovery of the link of diseases to chromosome abnormalities...
in 1963. The condition affects an estimated 1 in 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio.
Signs and symptoms
The syndrome gets its name from the characteristic cry of affected infants, which is similar to that of a meowing kitten, due to problems with the larynx and nervous system. About 1/3 of children lose the cry by age 2. Other symptoms of cri du chat syndrome may include:- feeding problems because of difficulty swallowing and sucking.
- low birth weightLow birth weightLow birth weight is defined as a birth weight of a liveborn infant of less than 2,500 g. regardless of gestational age-Causes:LBW is either the result of preterm birth or of the infant being small for gestational age , or a combination of...
and poor growth. - severe cognitive, speech, and motor delays.
- behavioral problems such as hyperactivity, aggression, tantrums, and repetitive movements.
- unusual facial features which may change over time.
- excessive droolingDroolingDrooling is when saliva flows outside the mouth...
. - constipation.
Other common findings include hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
, growth retardation, a round face with full cheeks, hypertelorism
Hypertelorism
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits . In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal...
, epicanthal folds, down-slanting palpebral fissure
Palpebral fissure
Palpebral fissure is the anatomic name for the separation between the upper and lower eyelids. In adults, this measures about 10mm vertically and 30mm horizontally.It can be reduced in horizontal size by fetal alcohol syndrome and in Williams Syndrome...
s, strabismus
Strabismus
Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...
, flat nasal bridge, down-turned mouth, micrognathia, low-set ears, short fingers, single palmar creases, and cardiac defects (e.g., ventricular septal defect
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
[VSD], atrial septal defect
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
[ASD], patent ductus arteriosus
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
[PDA], tetralogy of Fallot
Tetralogy of Fallot
Tetralogy of Fallot is a congenital heart defect which is classically understood to involve four anatomical abnormalities...
). People with Cri du chat are fertile and can reproduce.
Less frequently encountered findings include cleft lip and palate, preauricular tags and fistulas, thymic dysplasia, intestinal malrotation
Intestinal malrotation
Intestinal malrotation is a congenital anomaly of rotation of the midgut...
, megacolon
Megacolon
Megacolon is an abnormal dilation of the colon . The dilatation is often accompanied by a paralysis of the peristaltic movements of the bowel...
, inguinal hernia
Inguinal hernia
An inguinal hernia is a protrusion of abdominal-cavity contents through the inguinal canal. They are very common , and their repair is one of the most frequently performed surgical operations....
, dislocated hips, cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
, hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
, rare renal malformations (e.g., horseshoe kidneys, renal ectopia
Renal ectopia
Renal ectopia or ectopic kidney describes a kidney that is not located in its usual position. It results from the kidney failing to ascend from its origin in the true pelvis or from a superiorly ascended kidney located in the thorax....
or agenesis, hydronephrosis
Hydronephrosis
Hydronephrosis is distension and dilation of the renal pelvis calyces, usually caused by obstruction of the free flow of urine from the kidney, leading to progressive atrophy of the kidney...
), clinodactyly
Clinodactyly
-References:...
of the fifth fingers, talipes equinovarus, pes planus, syndactyly
Syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...
of the second and third fingers and toes, oligosyndactyly, and hyperextensible joints. The syndrome may also include various dermatoglyphics, including transverse flexion creases, distal axial triradius, increased whorls and arches on digits, and a single palmar crease.
Late childhood and adolescence findings include significant intellectual disability, microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
, coarsening of facial features, prominent supraorbital ridges, deep-set eyes, hypoplastic nasal bridge, severe malocclusion
Malocclusion
A malocclusion is a misalignment of teeth or incorrect relation between the teeth of the two dental arches. The term was coined by Edward Angle, the "father of modern orthodontics", as a derivative of occlusion, which refers to the manner in which opposing teeth meet.-Presentation:Most people have...
, and scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
.
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 uterus
Bicornuate uterus
A bicornuate uterus or bicornate uterus, commonly referred to as a "heart-shaped" uterus, is a type of uterine malformation where two "horns" form at the upper part of the uterus.-Pathophysiology:A bicornuate uterus is formed during embryogenesis....
. In males, testes are often small, but spermatogenesis is thought to be normal.
Genetics
Cri du chat syndrome is due to a partial deletion of the short arm of chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
number 5, also called "5p monosomy". Approximately 90% of cases results from a sporadic, or randomly-occurring, de novo deletion. The remaining 10-15% are due to unequal segregation of a parental balanced translocation where the 5p monosomy is often accompanied by a trisomic portion of the genome. These individuals may have more severe disease than those with isolated monosomy of 5p.
Most cases involve total loss of the most distant 20-10% of the material on the short arm. Fewer than 10% of cases have other rare cytogenetic aberrations (e.g., interstitial deletions, mosaicisms, rings and de novo translocations). The deleted chromosome 5 is paternal in origin in about 80% of de novo cases.
Loss of a small region in band 5p15.2 (cri du chat critical region) correlates with all the clinical features of the syndrome with the exception of 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. Two genes in these regions, Semaphorine F (SEMA5A) and delta catenin
Delta catenin
Delta-1-catenin and Delta-2-catenin are members of a subfamily of proteins with ten Armadillo-repeats. Delta-2-catenin is expressed in the brain where it is important for normal cognitive development. Like beta-catenin and gamma-catenin, delta-catenins seem to interact with presenilins...
(CTNND2), are potentially involved in cerebral development. The deletion of the telomerase reverse transcriptase
Telomerase reverse transcriptase
Telomerase reverse transcriptase is a catalytic subunit of the enzyme telomerase. Its absence is associated with the disorder Cri du chat....
(hTERT) gene localized in 5p15.33 may contribute to the phenotypic changes in cri du chat syndrome as well.
Diagnosis and management
Diagnosis is based on the distinctive cry and accompanying physical problems. Genetic counselingGenetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
and genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
may be offered to families with individuals who have cri du chat syndrome. Prenatally the deletion of the Cri du chat related region in the p arm of chromosome 5 can be detected from amniotic fluid or chorionic villi samples with BACs-on-Beads technology. Children may be treated by speech, sound, and occupational therapists. Cardiac abnormalities often require surgical correction.