Overview

Human chromosomes represent the format in which DNA is organised within the cells. They are numbered and loaded with all the information needed to make up an individual. Genetic syndromes can be caused by alterations in chromosome structure or composition.¹ Cri du Chat syndrome is caused by a deletion in chromosome 5, which means this specific chromosome is missing a fragment. It presents a characteristic elongated face, as well as intellectual delay. From French, Cri du Chat translates into “cry of the cat”. Its name comes from the main clinical sign of the syndrome, newborns who present a high-pitched cry, resembling a cat. Within a particular region of chromosome 5, a variety of fragment sizes can be missing, and although characterised as the same syndrome, they can show different symptoms and progression.²

It is common, and even characteristic, for individuals with Cri du Chat syndrome to have hearing-related symptoms, especially hypersensitivity. Hearing loss is not well documented, but its occurrence is considered common.³

Cri du chat syndrome

Genetic material carries all the information needed for an organism to exist and manage itself. It is coded as DNA, a molecule that safely holds hereditary features, also known as genes. DNA is present in almost every cell of the human body, and for that to be possible, it is condensed as chromosomes. Chromosomes are numbered and keep the information concentrated, organised and easy to access. Each chromosome has a variety of information. Chromosomes are usually X-shaped, allowing the observation of four arms. These arms may have different proportions and, based on that, they are named either short arms or long arms. Short arms are also identified as p arms, and long arms are also called q arms.⁴

Cri du Chat is a genetic syndrome also named 5p syndrome, because it is caused by a missing part in the short arm of chromosome 5. When a chromosome is missing a fragment, it is also called deletion.² 

Deletion is a type of mutation in which the genetic material is slightly altered from what is considered normal. Mutations can be inherited from parents; it happens in around 10% of Cri du Chat cases, but most are not hereditary. In these cases, mutation happens during embryo development. It means that, in early stages of pregnancy, when the soon-to-be fetus is still a cluster of growing cells, a part of chromosome 5 goes missing. Reasons are unknown.² 

Symptoms and characteristics 

• High-pitched cry resembling a cat 
• Intellectual disability 
• Delayed development 
• Hearing hypersensitivity
• Physical features (e.g., microcephaly, low birth weight) 

Diagnosis

• Clinical observations: identifying relevant signs such as cat-like crying, hypotonia (low muscle tone), elongated face, microcephaly;
• Genetic testing: the confirmation exam.

Hearing loss in cri du chat syndrome

Cri du Chat is not usually a direct cause of deafness, but there are reports on hearing impairments observed in these patients, with a varying range of severity. Although not an established hallmark, it is not considered uncommon when hearing loss is observed in individuals with that syndrome.

Possible causes of hearing loss

Underdeveloped anatomy

Some researchers believe that within the short arm of chromosome 5, there may be a gene responsible for the development of anatomic parts of the auditory system. If this is the case, the characteristic deletion in chromosome 5would be the cause of a hearing dysfunction.^3,5

Auditory neuropathy

Another type of hearing loss has been reported for individuals with 5p syndrome and differs from those that suggest deafness due to the missing gene responsible for anatomic parts of the auditory system. An individual may be able to perfectly receive sound within the ear, but have an impairment in the transmission of that information to the responsible parts of the brain. In that case, the person is unable to fully hear, but for different reasons, as the ears are anatomically normal. This is called an auditory neuropathy, in which the brain does not correctly process sounds. 

For some individuals, reports of poor communication skills that were attributed to cognitive delay may be hiding an auditory neuropathy. These cases are related to difficulty in speech understanding, a common feature of auditory neuropathy, while cognitive skills are not as delayed as expected by such observations.³   

Diagnosis and assessment of hearing loss

Hearing loss evaluation is recommended in all newborns. Ideally, by 6 months of age, all individuals should have gone through evaluation and started intervention if needed. 

Two main tests are typically applied for newborns. The otoacoustic emissions (OAE) and the automated auditory brainstem response (AABR). OAE detects movements from hair cells within the inner ear in response to sound stimuli. The hair cells are an important intermediate between receiving the stimuli in the ear and transforming them into a signal to the brain. AABR assesses the electrical signs emitted from different parts of the ear, which are responsible for carrying sound information to the brain. Newborns, before leaving the hospital, usually undergo OAE. For those with a risk of hearing complications, AABR is performed.⁶ 

Even after these first evaluations, parents are advised to keep monitoring and request ongoing assessments. When the child presents signs of hearing difficulty, a multi-disciplinary approach might be needed, involving an audiologist, otolaryngologist, paediatrician and even a geneticist⁶. 

Further assessments

Besides the newborn testing, other diagnostic tools can provide richer information if required. A few of the current available are:⁶

• Tympanometry: specific assessment of the tympanic membrane
• Pure-tone audiometry: through a headphone, the individual identifies sounds of varying frequencies and intensities
• Behavioural: The child reacts to sounds by moving the head in the direction from which they came

FAQs

Is cri du chat syndrome inherited from parents?

It can be, but most cases aren’t. The mutation that causes Cri du Chat syndrome usually occurs randomly during embryonic or fetal development. Only 10% of cases are an inheritance from unaffected parents. It happens when the parent carries a slight genetic alteration, which does not manifest in them, but can cause the specific deletion when passing its content to their child. Although invisible to the parent, the genetic alteration becomes unstable during embryo development, when the genetic material is being processed. Then it can cause the loss of part of the arm in chromosome 5, leading to the manifestation of the syndrome in the new generation.²

Does cri du chat syndrome cause hearing loss?

Not always. Hearing loss can happen in individuals with Cri du Chat syndrome, and proper diagnosis must be done to improve their quality of life. Hearing impairments are more common than hearing loss, but most cases point to a functioning auditory system. Cases of hearing loss are considered common for that syndrome and, sometimes, are misdiagnosed as a lack of communication skills. When speech understanding does not match expectations after auditory evaluation, that could be a sign of hearing loss due to the part of the brain that processes sounds being defective.³ 

What is the importance of early assessment of hearing loss?

Auditory stimuli are important during the early stages of development. Not knowing that a child is experiencing hearing loss can affect quality of life, school performance, and communication skills, and lead to psychological suffering. Early identification of auditory impairments enables better adaptation and improves the child’s capacity to express themselves.⁶ 

Summary

Cri du Chat or 5p syndrome is caused by the deletion of the short arm of chromosome 5. The missing fragment of the chromosome is supposed to carry important genes that, when lacking, will manifest the signs of the syndrome. Signs, symptoms, severity and prognosis depend on the size of the deletion. Individuals are usually first identified when their newborn's cry resembles a high-pitched cat cry. Genetic testing can confirm the diagnosis. Due to Cri du Chat, individuals usually present delayed intellectual development and cognitive abilities. They are usually sensitive to auditory stimuli. Hearing loss in these patients, although not well documented, is possible. It can happen either by a fault in the development of the anatomic parts of the ear or due to a dysfunction of the brain in recognising and processing sounds.