Introduction

First reported in 1831 by French physician Combettes, Cerebellar Agenesis (CA) is a condition where a person is born without their cerebellum… but, what does that mean?¹

What is the cerebellum?

The word “cerebellum” comes from a Latin word meaning “little brain”, and that’s exactly what it is. Located at the lower back of your brain, it is mostly responsible for movement, language and emotional control.²

Specifically, it helps to regulate voluntary movement and control our balance (for example, your posture and your gait are controlled by the cerebellum). In particular, a worm-like structure that connects the two halves of the cerebellum, called the “vermis,” moderates movement in the neck, shoulders, hips and abdomen; while the outer layers of each half are responsible for planning, correcting and coordinating movement.³

So, what causes Cerebellar Agenesis?

Agenesis refers to an organ being undeveloped, with one proposed cause of CA being a mutation in the PTF1A gene at birth.^4,5 Additionally, infection in the womb can cause acquired CA (as opposed to it being an inherited condition); however, this is usually seen alongside other conditions.⁶ There have only been ten reported cases of CA prior to 1998, making it an incredibly rare condition.⁷ Each of these cases, however, has been recorded at various ages, with the condition being lifelong.⁸

Due to the cerebellum playing a key role in our motor skills, people with CA usually experience difficulty with movement, dexterity and a delay in articulation. The specific symptoms experienced by people living with CA can vary, thus creating a clinical spectrum for the condition.^9,10

The Varying Degrees of Cerebellar Agenesis

The “clinical spectrum” of a condition simply refers to how severely it manifests in the people who have it; as such, this article will go into further detail regarding just how different CA can be in each case.

Asymptomatic CA

You may have heard the term “asymptomatic” before; while tricky to visualise, it means being ill but having no symptoms, like having a cold without a runny nose.

Before 1994, there had been widespread belief that CA could be asymptomatic; however, a review published that year found that there hadn’t been a single documented case of complete CA without some recorded motor difficulties.¹¹ However, a less severe instance of CA was observed in a 58-year-old woman who still had part of her cerebellum; as a result, she faced no neurological difficulties. This meant that despite experiencing partial CA, she had no observable symptoms.¹² So, for CA to be asymptomatic, the person living with the condition must still have a partially developed cerebellum, but the absence of obvious symptoms can make it a lot harder to detect. Typically, doctors will conduct a series of tests to assess your mental activity and behaviour; however, when these came back as normal for the 58-year-old woman (whose only symptom at this point has been headaches), they conducted an MRI scan. The image produced is what led to her diagnosis of subtotal CA. Due to the near-complete absence of symptoms, the patient received no known treatment, as asymptomatic CA doesn’t appear to impact daily life too much.¹³

Mild to Moderate CA

In many cases of CA, it has been found that the rest of the brain attempts to compensate for the absence of the cerebellum. This leads to the development of some movement and a slightly less severe presentation of the condition.⁷ These instances of CA are considered mild to moderate cases. 

Common symptoms of moderate CA include:

• Muscle weakness that causes slurred speech
• Some issues with balance and coordination in the limbs 
• Difficulty in coordinating voluntary movements
• An increase in voluntary tremors when making intentional movements

These symptoms were all present in a 59-year-old woman who was only diagnosed following an MRI taken for a separate issue. However, her medical history showed many signs of mild CA from birth: she had a history of clumsiness, was delayed in her motor development (learning to walk at age three) and her speech was slurred. As she grew older, these symptoms - especially her movement and coordination - seemed to improve, only becoming worse after a hip replacement. What’s more, she was able to lead a mostly independent lifestyle with little cognitive impairment. Ultimately, the symptoms did persist as she experienced difficulty with more detail-oriented tasks as a result of cognitive and coordination struggles. The overall scope of her abilities was detected using a range of neurological tests. One in particular, called a fingers-to-nose test, was able to reveal the aforementioned tremor.¹⁴

Treatment for mild CA may involve various therapies that aim to improve speech, dexterity and overall movement. Due to the rarity of cases, there is no single established treatment.¹⁵

Severe CA

The most extreme or severe cases of CA typically present with a complete absence of the cerebellum and are typically reported in children. Symptoms they may experience (including those previously listed) include epilepsy, a buildup of fluid in the brain and severe mental impairment. If an infant displays neurological delay, they may be diagnosed with a scan, but many cases of complete CA have been undiagnosed until autopsy. Unlike milder cases of CA, the severity of symptoms that result in severe motor underdevelopment may not be impacted by physical therapies; as such, no definitive treatment for complete or severe CA exists.¹⁶

Life with CA

The majority of reported CA cases appear to fall between mild to severe, with people experiencing extreme deficits in movement and coordination. However, while greatly impacting the quality of their lives, CA hasn’t been shown to impact life expectancy, with some people experiencing an improvement in mobility as they age.^12,17

As prenatal testing improves, CA can be detected in the womb via an ultrasound. This gives families the option to access any support available and become fully prepared to care for a loved one with CA.¹⁸ Often, CA presents alongside other conditions that seriously impact the development of the nervous system, providing further challenges.⁷

Despite its rarity, some conditions are similar to CA:

• Cerebellar hypoplasia - a generic term describing a cerebellum with a decreased volume
• Dandy-Walker syndrome - a condition where some parts of the cerebellum are missing, and others are filled with fluid
• Joubert syndrome - a condition affecting the brainstem and the vermis

These conditions can all be distinguished from one another using CT or MRI scans.^8,19,20

Summary

Cerebellar agenesis is a condition where someone is born with either a partial or completely missing brainstem. Cases of CA are rare, with the severity of symptoms varying from little to no impairment to extreme difficulty with movement, balance, cognition, speech and fine motor tasks. Detecting and diagnosing CA can be done via a number of neurological exams and is often confirmed with a CT or MRI scan. Following this, treatment is usually aimed at alleviating the difficulty brought on by symptoms. People with CA may engage with physical therapy to help improve balance and voluntary movement, and some might undergo speech therapy to prevent slurring when talking. It is a condition bound to impact most aspects of a person’s life; however, many people with CA are capable of living independently with minimal difficulty. 

Ultimately, CA is a fascinating but challenging condition, affecting fewer than 20 people worldwide.

FAQs

What is Cerebellar Agenesis?

A complex neurological condition characterised by a partial or complete absence of the cerebellum.

How likely are you to have it?

Not very, cases are extremely rare, with approximately ten being reported since 1998.

Why is the cerebellum important?

It is responsible for a lot of our conscious movement and cognitive skills, such as memory, planning and language.²¹ 

How can Cerebellar Agenesis be treated?

CA treatment is typically focused on symptoms, so people with the condition may benefit from physical therapy to help with movement or speech therapy to help with any language difficulties they may have.¹⁵