2History In 1963, Lejeune et al., High-pitched. Microcephaly. Growth failureAbnormal face..Mental retardationFacial abnormalities.Multiple congenital anomalies.
3Frequency incidence 1 in 50,000 livebirths. 1.5 in 1000 among individual with mental retardation.Mortality/Morbidity75% die within the first few months of life.90% die before they are aged 1 year.Survival to adulthood is possible.RaceNo known racial predilection exists.SexMale:Female ratio of 0.72.
4MechanismMost cases (80-85%) are due to sporadic de novo deletion of 5p.30-60% of the cases involve terminal deletions with loss of 5p material.Approximately 10-15% of cases result from the unequal segregation of a parental balanced translocation where the 5p monosomy is often accompanied by a trisomic portion of the genome.Fewer than 10% of cases have other rare cytogenetic aberrations (eg, interstitial deletions, mosaicisms, rings and de novo translocations).The deleted chromosome 5 is paternal in origin in about 80% of the cases.
11Less frequently findings Hypospadias,Inguinal hernia.Dislocated hips.Cryptorchidism.Gut malrotation.Hydronephrosis.Thymic dysplasia.Cleft lip and palate.Talipes equinovarus.Renal ectopia or agenesis.Preauricular tags and fistulas.Clinodactyly of the fifth fingers.Oligosyndactyly, and hyperextensible joints.Rare renal malformations (horseshoe kidneys).Syndactyly of the second and third fingers and toes.
12Causes of death Pneumonia. Aspiration pneumonia. Congenital heart defects.Respiratory distress syndrome.
13Behavioral history Behavioral profile includes Aggression. Clumsiness. Hyperactivity.Repetitive movements.Hypersensitivity to sound.Stereotypic and self-injurious behavior.Features similar to those of autism
14Image is of an infant with cri-du-chat syndrome Image is of an infant with cri-du-chat syndrome. Note a round face with full cheeks, and apparently low-set ears
21Fluorescence in situ hybridization In patients with very small deletions.The absence of a fluorescent signalfrom either the maternal or paternalchromosome 5p regions is indicative ofmonosomy for that chromosomal region.Region-specific probe
22Absence of a green signal indicates monosomy for that region (left, interphase cell; right, metaphase chromosome spread).Green is cri-du-chat locus signal.Orange color represents chromosome 5–specific signal
23Late childhood and adolescence Findings includeDeep-set eyes.Hypoplastic nasal bridge.severe mental retardation.Coarsening of facial features.Prominent supraorbital ridges.Severe malocclusion and scoliosis.
24At puberty Female Males Menstruate at the usual time. The genital tract is normal in females.Develop secondary sex characteristics.MalesTestes are often small.Spermatogenesis is normal.
25Consultations Dentist. Urologist. Audiologist. Neurologist. Orthopedist.Cardiologist.Psychologist.Ophthalmologist.Clinical geneticist.Developmental pediatrician.Speech language pathologist.Physical and occupational therapist.
26Genetic counseling Risk should be assessed based on the type of structuralrearrangement and its patternof segregation
27Genetic counseling Recurrence risk for affected female is 50%. Recurrence risk for a de novo case is 1%.If a parent is a balanced carrier of a structuralrearrangement, the risk is substantially high.Rare recurrences in chromosomally normalparents result of gonadal mosaicism for the5p deletion in one of the parents.
28Prenatal diagnosis Amniocentesis Routinely performed at 14-16 weeks’ gestation. Testing for chromosome disordersis 99.5% accurate. The missed are cases of mosaicism. The procedure is associated with asmall risk of pregnancy loss (about1 in ).
29Chorionic villus sampling (CVS) TimingPerformed at weeks’ gestation.Limitation and risk1. Small chance of maternal cell contamination.2. Risk of a fetal loss after the procedure 0.5-1%. 3. Accuracy less than Amniocentesis(mosaicism maternal cell contamination).
30Percutaneous umbilical blood sampling (PUBS) Is of limited use, except in cases dated late in pregnancy.
31Medical Legal Pitfalls Failure to:Recognize characteristic symptoms and signs.Refer to a geneticist for genetic counseling.Request chromosome analysis of patients with the clinical phenotype of cri-du-chat.Request chromosome analysis of parents to rule out familial translocation.Offer prenatal diagnosis after the birth of an affected child.
32PrognosisActivityActivities are limited because of profound mental retardation andphysical handicaps.Patient EducationFamilies are greatly affected.The main contributor to increased family stress is thechild's maladaptive behavior. However, these familiesalso receive social support from other families, friends,and concerned professionals.
33Surgical Care Correction of congenital heart defects may be indicated. Orchiopexy for undescended testes.Issues important to anesthetic plan:Hypotonia.Temperature maintenance.Anatomical abnormalities of the airway.Mental retardation Congenital heart disease.
35Imaging Studies: Skeletal radiography Microcephaly, retromicrognathia Cranial base malformations (reduced cranial base angle and malformed sella turcica and clivus)Disproportionately short third, fourth, and fifth metacarpals and disproportionately long second, third, fourth, and fifth proximal phalanges (frequent)
36Laryngeal appearance Floppy epiglottis. Small larynx. Asymmetric vocal cords.However, the cause of the characteristic cry cannot be entirely ascribed to the larynx. A developmental field connecting the brain and the affected clivus region of the cranial base with the laryngeal region from which the characteristic cry derives may exist. This area of the brain is probably deformed in patients with cri-du-chat syndrome. The characteristic cry usually disappears with time.
37Magnetic resonance imaging Atrophy of the brainstem, atrophic middle cerebellar peduncles and cerebellar white matterPossible hypoplasia of cerebellar vermis with enlargement of the cisterna magna and fourth ventricleEchocardiography - To rule out structural cardiac malformationsOther Tests:Swallowing study for feeding difficultyComprehensive evaluation for receptive and expressive language: Most children have better receptive language than expressive language.Developmental testing, referral to early intervention, and appropriate school placement
38Childhood findings Include severe mental retardation Developmental delayMicrocephalyHypertonicityPremature graying of the hairDropped-jaw, open-mouth expression secondary to facial laxity; short philtrum; malocclusion of the teeth; scoliosis; short third-fifth metacarpals; and chronic medical problems such as upper respiratory tract infections, otitis media, severe constipation, and hyperactivity.