Cri-du-chat syndrome is a rare chromosomal disorder that is present from birth. The name, cri du chat, is French for “cry of the cat,” and it refers to the characteristic high-pitched cry heard in affected infants, which is caused by an abnormal development of the larynx (voice box). The clinical name for the condition is 5p- Syndrome, which describes the underlying genetic cause.

To understand what happens, it is helpful to use an analogy. Think of your complete set of 46 chromosomes as a 46-volume encyclopedia containing all the instructions for building and running the human body.

• Each volume is essential and contains thousands of “recipes” or genes.
• In Cri-du-chat syndrome, it is as if a section of pages, a small but important chapter has been accidentally torn out and lost from the first part (the “p” arm) of Volume #5.
• The loss of these specific genetic recipes disrupts the normal developmental plan for several body systems. This has the most significant impact on the development of the brain, leading to intellectual and motor challenges, and on the larynx, causing the characteristic cry.

In my experience, the characteristic high-pitched cry of affected newborns often prompts early concern. Parents usually sense something is different right from birth.

The direct cause of Cri-du-chat syndrome is a chromosomal deletion. Specifically, there is a missing piece from the end of the short (p) arm of chromosome 5.

The size of this deleted segment can vary among individuals with the syndrome, which can sometimes influence the severity of the associated symptoms. Researchers have been able to map specific genes within this deleted region to particular features of the syndrome. For example, the loss of a gene called CTNND2 is thought to be strongly associated with the severity of the intellectual disability seen in the condition.

In my experience, some families carry a balanced translocation, so I always recommend parental karyotyping to assess recurrence risk in future pregnancies.

Cri-du-chat syndrome is a chromosomal condition that arises from an error in the genetic material. It is not contagious and cannot be acquired after birth. The way this error occurs is a crucial point of understanding for families.

• Sporadic (de novo) Deletion: In the vast majority of cases (approximately 85-90%), the deletion is a sporadic, or de novo, event. This means the loss of the piece of chromosome 5 is a new, random error that occurred during the formation of either the egg or the sperm cell in a healthy parent, or that happened very early in embryonic development. In these cases, the parents have normal chromosomes, and there is absolutely nothing they did or did not do before or during the pregnancy to cause the condition. It is a random biological accident.
• Inheritance from a Parent with a Translocation: In about 10-15% of cases, the deletion can be the result of a parent carrying a balanced translocation. In a balanced translocation, a parent has all of their genetic material, but a piece of one chromosome has broken off and attached to another chromosome. Because the parent is not missing any genetic information, they are perfectly healthy. However, they are at a higher risk of producing an egg or sperm cell that has an unbalanced amount of genetic material, in this case, an egg or sperm that is missing the end of chromosome 5. If this cell is involved in conception, the resulting child will have Cri-du-chat syndrome.

For this reason, when a child is diagnosed with Cri-du-chat syndrome, the parents are always offered a blood test (a karyotype) to check their own chromosomes to see if one of them is a carrier of a balanced translocation. This is very important for providing accurate genetic counseling about the risk in future pregnancies.

In my experience, most cases arise spontaneously, without any known cause or family history, although parental chromosomal abnormalities can sometimes be involved.

Individuals with Cri-du-chat syndrome have a recognizable pattern of physical, developmental, and intellectual characteristics, although the severity can vary.

The Hallmark Sign:

• The “Cat-like” Cry: A very high-pitched cry in infancy that sounds like a kitten mewing is the most characteristic and well-known feature. This cry is due to an underdeveloped larynx and typically becomes less noticeable as the child gets older.

Craniofacial Features: Many children with the syndrome share a distinctive facial appearance.

• Microcephaly: An abnormally small head size at birth.
• A round face with full cheeks.
• Widely spaced eyes (hypertelorism).
• Downward-slanting eyes.
• A small jaw (micrognathia) and a small chin.
• Low-set ears.

Growth and Physical Development:

• Low birth weight is common.
• Poor growth in infancy and childhood (failure to thrive) is a nearly universal feature.
• Hypotonia: Very low muscle tone, or “floppiness,” is present in infancy. This contributes to significant feeding difficulties and delays in reaching motor milestones.

Developmental and Intellectual Challenges:

• Intellectual Disability: All individuals with Cri-du-chat syndrome have some degree of intellectual disability, which is typically in the moderate to severe range.
• Developmental Delays: There are significant delays in all areas of development.
  • Motor Delays: Due to the hypotonia, milestones like sitting, crawling, and walking are significantly delayed.
  • Speech and Language Delays: This is a major area of challenge. While many individuals can understand language well, their ability to produce verbal speech is often very limited.

Other Medical Issues:

• Congenital heart defects are present in some children.
• Skeletal problems, such as curvature of the spine (scoliosis), can develop.
• Vision and hearing problems can also occur.

Clinically, I monitor for delayed milestones, intellectual disability, and motor coordination issues. Some children may also have congenital heart defects or feeding difficulties.

A diagnosis of Cri-du-chat syndrome is usually suspected shortly after birth based on the baby’s distinctive clinical features.

• Clinical Suspicion: The primary clue is the unmistakable high-pitched, cat-like cry. This, combined with a small head size and other characteristic facial features, will prompt a pediatrician to recommend a genetic evaluation.
• Chromosome Analysis: The diagnosis is definitively confirmed with a chromosome analysis from a blood sample.
  • Karyotype: This is a standard test where the chromosomes are stained and visualized under a microscope. The karyotype will clearly show the missing portion of the short (p) arm of one of the chromosome 5s.
  • Fluorescence In Situ Hybridization (FISH) or a Chromosomal Microarray: These are more advanced genetic tests that can be used to precisely identify the boundaries of the deletion and determine exactly how much genetic material is missing.

Once a diagnosis is confirmed, a child will undergo a comprehensive evaluation to screen for associated medical problems, including an echocardiogram to check the heart and formal hearing and vision tests.

In my experience, early diagnosis is key for enrolling the child in developmental and educational support programs tailored to their needs.

There is no cure for Cri-du-chat syndrome, as the missing genetic material cannot be replaced. Management is a lifelong, supportive process focused on helping the child reach their maximum developmental potential and on managing their specific health and educational needs. This requires a dedicated and coordinated multidisciplinary team.

Early Intervention Therapies: The Cornerstone of Management

This is the most important part of the management plan for a child with Cri-du-chat syndrome. An intensive program of therapies started as early as possible can have a profound impact on a child’s development.

• Physical Therapy: This is crucial from infancy to address the low muscle tone, help with head control, and work toward achieving motor milestones like sitting, crawling, and walking.
• Occupational Therapy: This helps with fine motor skills, sensory processing issues, and learning the skills needed for daily living, such as feeding and dressing.
• Speech and Language Therapy: This is essential to address the significant communication challenges. Because verbal speech may be very limited, therapy often focuses on total communication. This includes teaching sign language, using picture exchange communication systems (PECS), or utilizing electronic communication devices to give the child a way to express their wants and needs.

Educational Support

Children with Cri-du-chat syndrome will require an individualized education plan (IEP) and a supportive, specialized school environment throughout their lives to meet their unique learning needs.

Medical Management

• Nutritional Support: A nutritionist or feeding specialist may be needed to manage the feeding difficulties in infancy and ensure adequate calorie intake for growth.
• Routine Care: Regular check-ups with a pediatrician and other specialists are needed to monitor for and manage any associated health issues, such as heart problems, scoliosis, or hearing and vision problems.

I focus on multidisciplinary support, physical therapy, speech therapy, special education, and regular pediatric follow-up for optimal developmental outcomes.

A diagnosis of Cri-du-chat syndrome brings a family into a world of unique challenges and lifelong care. This rare chromosomal disorder, caused by a deletion on chromosome 5, results in a distinct set of physical features and significant developmental and intellectual disabilities. While there is no cure, it is crucial to remember that this is not a degenerative disease. The journey is not one of regression, but of slow, steady progress. A correct diagnosis provides a roadmap, allowing families to access the essential services their child needs. The cornerstone of care is a deep commitment to intensive early intervention. Through the dedicated work of physical, occupational, and speech therapists, and with the unwavering love, patience, and advocacy of their families, children with Cri-du-chat syndrome can learn, grow, and communicate. Clinically, I find that compassionate guidance, family education, and coordinated care make a significant difference in long-term quality of life for both the child and caregivers.

National Organization for Rare Disorders (NORD). (2023). Cri du Chat Syndrome. Retrieved from https://rarediseases.org/rare-diseases/cri-du-chat-syndrome/

National Institutes of Health, Genetic and Rare Diseases Information Center (GARD). (2023). Cri-du-chat syndrome. Retrieved from https://rarediseases.info.nih.gov/diseases/6211/cri-du-chat-syndrome

The 5p- Society. (n.d.). What is 5p- Syndrome? Retrieved from https://www.fivepminus.org/