Overview

Cri du chat syndrome (CdC) is a rare genetic disorder caused by partial deletion of chromosome 5. There are notable symptoms associated with CdC with information relating to children more common than for adults, but the genetic mutations responsible occur early in embryonic development and many of these carry over into adulthood.

“Cri du chat” is a French word meaning “cat’s cry”, used since babies born with this condition tend to exhibit crying similar to a kitten. This disappears after the first few weeks of life.

The words hypoplasia and hypoplastic are used throughout this article, medical terms referring to underdevelopment or diminished formation of organs or part of organs.

Physical symptoms that carry over from childhood

Children exhibit the “full range” of CdC symptoms with many disappearing as you get older, but there are still several physical ones that large proportions of adults have:

• Hypertelorism
• Microretrognathia
• Hypoplasia of the thenar eminence

These are the physical symptoms impacting or causing difficulty in those with CdC and are not merely appearance-based.¹

Hypertelorism

Hypertelorism refers to an abnormally longer distance between two body parts, typically the eyes, like in the context of CdC. As well as being visually noticeable, sufferers may find it difficult to focus on objects close to them – this is known as convergence insufficiency. Aside from this, people with hypertelorism do not generally have any other vision problems.²

Micrognathia

Micrognathia refers to the underdevelopment of the jaw, making it smaller than average. Since this occurs during embryonic development, the proportion of the jaw to the rest of the head remains the same after birth, meaning that micrognathia often prevails into adulthood. Micrognathia can cause difficulties in chewing and swallowing along with disrupted breathing during sleep (known as sleep apnoea).

The malformation of the jaw may also cause improper dental growth due to limited space within the mouth and the risk of periodontal disease since many areas may be difficult to reach when brushing teeth. Speech problems are common but vary in severity depending on the degree of the abnormality.

A similar condition known as microretrognathia is where the jaw is positioned further back than normal, making the micrognathia more challenging.

Hypoplasia of the thenar eminence

The thenar eminence refers to a group of muscles on the palm that are responsible for thumb motion. CdC patients may have hypoplasia of the thenar eminence, which is incorrect, and underdevelopment of these muscles. This can make thenar eminence physically smaller in appearance, but more importantly hinders daily tasks such as holding items and writing, limiting independence.

In addition, the muscle function (hypoplasia) can affect nerve connections to the fingers and the rest of the hand. This can affect overall hand strength as pain or numbness may be experienced. Reduced usage of the muscles in the thenar eminence can lead to atrophy, or wasting away, reducing them in size even further.

Dental problems

As mentioned earlier, micrognathia can affect teeth, causing non-alignment (referred to as malocclusions). The most notable setback this can cause is difficulty brushing teeth, meaning stains, cavities and infections have the potential to arise over time.³ Dentist assistance may remove some of these issues temporarily, but this is not an efficient long-term solution.

If microretrognathia is present, overbite is likely, where the teeth from the maxilla (upper jaw) protrude significantly in front of the mandible (lower jaw). If the formation of the gums is uneven, the open bite may be present; this is where the teeth of both jaws form a gap when both jaws are brought together in a bite.

Micrognathia and micro retrognathia are both correctable via surgery, as are the various malocclusions mentioned above. This means while they cause large obstacles in day-to-day life, surgical intervention can fix most dental problems that persist in CdC adults.

Problems with eating

Bilateral polymicrogyria can affect neuronal connections to muscles in the throat, therefore causing hypertonia over time.

CdC does not only make it difficult to consume food but also to sense it adequately. The olfactory sulcus is a brain fold that houses the olfactory bulb, a collection of neurons important for the perception of smell and taste. Olfactory hypoplasia leads to the partial or total loss of these senses; as many tastes are reliant on odours, the loss of both is more common than just one of them.

Babies may also be born with agenesis (complete absence) of the olfactory bulb meaning they live without ever smelling or tasting foods, or at least at a very low sensitivity. Persisting into adulthood, can make adults demotivated or feel neutral regarding food habits, or in more negative cases, depressed.

Intellectual impairments

Many areas of the brain are affected due to CdC, including those involved in intellectual development; these may be responsible for certain cerebral functions or are important in transferring information.⁴

For the former, the middle cerebellar peduncles may be hypoplastic and neurons within the anterior limb of the anterior capsule may not be myelinated, reducing efficiency in electric impulse conduction. The result is poor and inconsistent signal networking across the brain.

With these neural abnormalities, it can be hard to process information, especially in communicating in a non-literal sense (e.g., use of metaphors or sarcasm) and the capability to make independent decisions is reduced.

Behavioural problems

The hypothalamus, responsible for feeling satisfaction as the “reward centre” of the brain, is impaired with CdC. As well as affecting motivation, there have been cases of recurrent aggressive behaviour including self-inflicting wounding. Hypothalamic stimulation using impulses has been shown to reduce this.⁵

Even though different parts of the brain are affected, behavioural issues have been compared to autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD).⁶

Walking and movement difficulties

While the development of limb muscles in those with CdC is not generally affected, the same cannot be said for the brain, whereby various regions are shown to be hypoplastic size reduction).⁷ Regions of the brain that develop with hypoplasia that are related to motion are:

• Cerebellar vermis, located in the middle of the two hemispheres (left and right halves)
• Cerebellum, a region located at the base
• Brainstem, connecting the rest of the brain to the spinal cord

Hypoplasia of both the cerebellum and cerebellar vermis is collectively referred to as Dandy-Walker malformation (DWM). This can affect movement and balance, but DWM is linked to a wider variety of symptoms such as seizures, stiff muscles and jerky movements.

Adults with CdC may not have hypoplasia in all these areas of the brain, however, a combination of their presence makes motion and coordination problems more likely, not necessarily worse.

The brainstem serves as the most direct connection between the brain and the spinal cord, whereby the latter contains many bundles of nerves that go to the muscles. Underdevelopment of the brainstem affects neuronal pathways before they reach the spinal cord, resulting in them either being damaged or all present.

As the muscles do not contract as often or efficiently as someone without CdC or any relevant condition affecting muscles, overtime this results in hypotonia, low muscle tone and tension. The diminished capability of these muscles leads to a “cycle” of difficulty and inability to contract these muscles effectively, creating more hypotonia.⁸

Altogether, the weakening of leg muscles can cause paralysis, but if someone has “normal” functionality while others do not this can create abnormal gait (walking patterns) and posture, the latter worsened with kyphoscoliosis - curving and hunching of the spine.⁷

Speech issues

Causes for problems with speech can be split into two categories: 

• Physical inability to communicate regarding the muscles and psychomotor function (the ability of the brain to process neuronal signals into muscles) 
• The cognitive ability to understand and use language

Speech development occurs later and at a slower rate in children with CdC compared to those without it. The cognitive component of delayed speech is less of a burden compared to the obstacles of talking, i.e., children with CdC can comprehend others, but may be able to verbally communicate at a later age.⁹

Speech therapy can help these problems go away, but if this type of treatment is not available to the child, and they continue to live without any support, these problems can last into adulthood. In these scenarios, it is not uncommon for adults with CdC to have these same speech impediments. ^[10] As mentioned before, these adults would likely be able to understand others’ speech despite their inability to communicate this way.

Summary

There are a variety of symptoms in adults who have cri du chat syndrome, ranging from prominent physical abnormalities to internal problems that can make day-to-day life more difficult than someone who does not have this condition. While most research is in children with cri du chat, a few of these symptoms persist into adulthood; these however are well-understood regarding their biological origin. Despite numerous factors that affect quality of life, there is as much understanding present to ensure proper guidance and support are available.