Cri du chat

Overview

Cri du chat syndrome, also known as 5p minus (5p–) syndrome, is a rare genetic disorder caused by a deletion of the short arm (p) of chromosome 5. The name "cri du chat" is French for "cry of the cat," referring to the high-pitched, cat-like cry that affected infants often produce. This syndrome is characterized by intellectual disability, delayed development, distinctive facial features, and low birth weight. It affects approximately 1 in 15,000 to 50,000 live births and is more common in females than in males.

Causes

Cri du chat syndrome is caused by a missing segment on the short arm of chromosome 5. This deletion may be:

• De novo (sporadic): Most cases (around 80–90%) occur spontaneously and are not inherited from parents.

• Inherited: In about 10–15% of cases, one parent carries a balanced chromosomal rearrangement (translocation) that increases the risk of passing on a deletion.

The specific genes deleted in this region contribute to the syndrome’s physical and cognitive characteristics, though not all have been clearly identified. Loss of the CTNND2 gene is thought to be linked to intellectual disability.

Symptoms

Symptoms and severity can vary widely among individuals but typically include:

• High-pitched cry: Resembling a cat, present in infancy and usually resolves with age

• Microcephaly: Small head size

• Distinctive facial features: Including widely spaced eyes (hypertelorism), a broad nasal bridge, a small jaw (micrognathia), and low-set ears

• Low birth weight and poor growth: Failure to thrive during infancy

• Hypotonia: Decreased muscle tone

• Delayed motor development: Late sitting, standing, and walking milestones

• Speech and intellectual disability: Ranging from moderate to severe; many children have limited verbal abilities

• Behavioral challenges: Including hyperactivity, repetitive movements, and tantrums

• Feeding difficulties: Due to poor suck or swallow reflexes

Diagnosis

Diagnosis of cri du chat syndrome is based on clinical features and confirmed through genetic testing. Diagnostic tools include:

• Physical examination: Identification of characteristic symptoms, particularly in infancy

• Karyotyping: Traditional chromosome analysis can detect large deletions on chromosome 5

• FISH (Fluorescence In Situ Hybridization): Used to detect smaller deletions not visible on karyotyping

• Microarray analysis: Offers high-resolution detection of chromosomal deletions

• Prenatal diagnosis: Possible through chorionic villus sampling (CVS) or amniocentesis if there's a known familial risk

Treatment

There is no cure for cri du chat syndrome, but early intervention and supportive therapies can improve outcomes and quality of life. A multidisciplinary care team is typically involved. Treatment strategies include:

• Speech therapy: To address communication delays

• Physical and occupational therapy: To support motor development and improve strength and coordination

• Special education programs: Tailored to meet intellectual and behavioral needs

• Behavioral therapy: To address attention difficulties, aggression, or anxiety

• Nutritional support: For feeding difficulties in infancy

• Medical management: Regular monitoring for potential complications such as scoliosis, vision or hearing issues, and heart or kidney abnormalities

Prognosis

The prognosis for individuals with cri du chat syndrome depends on the size and location of the chromosomal deletion and the severity of symptoms. With proper medical care and early intervention, many individuals can achieve improved communication, mobility, and social skills. Most people with the syndrome have significant developmental delays but can live into adulthood. Life expectancy is generally normal, though complications such as respiratory infections, feeding issues, or congenital anomalies may impact overall health in some cases.