Cerebellar hypoplasia, what is it?

Cerebellar hypoplasia, what is it?

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Cerebellar hypoplasia (HC) is a neurological condition characterized by problems in cerebellar development, it can include the vermis and / or the cerebral hemispheres. In this condition, the cerebellar volume reduction is typical, since an important part of the brain does not develop completely.

Cerebellar hypoplasia is a rare disorder among the population, there are several subtypes. Likewise, they may be related to other neurological syndromes and underlying disorders, so the variants in their clinical manifestation can be very diverse, making diagnosis and treatment difficult.

“The brain is the most fascinating object in the universe. Each human brain is different, makes each human being unique and defines who it is. ” Stanley B. Prusiner (Nobel Prize in Medicine, 1997).


  • 1 Histogenesis of the cerebellum and its importance
  • 2 Common clinical manifestations of cerebellar hypoplasia
  • 3 Etiology of cerebellar hypoplasia
  • 4 Types of cerebellar hypoplasia
  • 5 Phetocerebellar hypoplasia (HPC) phenotypes
  • 6 Cerebellar hypoplasia and some associated syndromes
  • 7 Cerebellar hypoplasia: Diagnosis and treatment

Histogenesis of the cerebellum and its importance

The brain is made up of: brain, cerebellum and medulla. The cerebellum is an essential structure of our nervous system, it is divided into two hemispheres, among them is the vermis, where the nerve endings carry messages for proprioception, which actively participates in the development of the body scheme and its spatial relationship, some of the functions of the proprioception they are: coordinate the range of movement, direction and balance among others, allowing automatic body responses.

The back of the brain, the cerebellum regulates muscle coordination, balance, maintenance of muscle tone, certain movements and speech; at the same time, it actively participates in complex cognitive processes such as: memory, language, executive functions and visospatial perception.

The cerebellum of the human being begins its development during the second month of gestation, from two wing planes, located in the rostral area of ​​the rhombencephalon. In the histogenesis of the cerebellar cortex, we find that in certain stages of development three layers are formed, in them you can see the definitive cerebellar maturity, from the surface to the interior they are: molecular layer (CM), Purkinje cell layer (CCP ) and layer of internal grains or granular cells (GCC).

Common clinical manifestations of cerebellar hypoplasia

By its nature, cerebellar hypoplasia can be progressive or static, the first does not have a prognosis as encouraging as the second. The survival of people with this condition is variable, since it depends on various factors and the severity of their clinical manifestations; In the Human Phenotype Ontology (HPO), we find the following:

Etiology of cerebellar hypoplasia

Cerebellar hypoplasia is usually associated with developmental chromosomal abnormalities, specifically during embryogenesis, causing uncommon genetic disorders with neurological repercussions. This developmental disorder is often inherited in an autosomal recessive manner and less commonly in an autosomal dominant or X-linked form.

Malformations of the cerebellum, can be very varied and for various reasons. Often, cerebellar hypoplasia (HC) may have its origin in a conjunction of genetic factors; as the pathological mutation of the Reelin gene, manufacturer of a protein called reelin, essential to regulate the positioning of brain development and neuronal migration processes.

In some subtypes of cerebellar hypoplasia (HC), abnormalities may be associated with atrophy in the cerebral cortex or tumors of the posterior fossa, which occur regularly in children, of which 60% are brain tumors and 40% develop specifically in the cerebellum. Cerebral hypoplasia may have its etiology in other clinical entities such as:

  • Stroke or vascular accidents.
  • Viral infections.
  • Toxic: exposure to toxins in utero.
  • Neurodegenerative diseases.
  • Dysgenesis: malformation.
  • Cerebellar artery agenesis: usually with an early intrauterine origin.

Types of cerebellar hypoplasia

Cerebellar hypoplasia, as the name implies, is limited to the cerebellum, however we can find a different typology, what does this depend on? From its etiology, the specific areas involved and those affected, underlying diseases, clinical manifestations and mutations in some genes. Some types of cerebellar hypoplasia (HC) are:

  1. Hemispheric or unilateral cerebellar hemisphere. Associated with a marked delay of motor development, it commonly has its etiology in vascular anomalies, either in cerebellar arteries or vertebral arteries. Likewise, they can be caused by malformations in the posterior fossa, or by a retrocerebellar cyst with stenosis of the Silvio aqueduct.
  2. Generalized 1. With the fourth enlarged ventricle Dandy Walker continued.
  3. With the fourth normal ventricle:
    1. normal fields
    2. with small
  4. Hypoplasia with Norman granular cells.
  5. Pontocerebellar hypoplasia (PCH).
  6. Syndromes with hypoplasia and cerebellar lissencephaly (LCH)
  7. Unidentified cerebellar hypoplasia.
  8. Pontocerebellar hypoplasia (HPC). It is related to brain, cerebellum, bridge, brain stem and intermediate areas, more than ten subtypes are known, their genotype-phenotype correlation and other aspects are still under study. Its classification depends on the gene, the brain areas involved and the intervention of various factors. There are cases of HPC associated with the mutation of several genes.
  9. Olivopontocerebellar hypoplasias. Congenital disorders of cerebral morphogenesis associated with various etiologies, include type 1 carbohydrate-deficient glycoproteins syndrome, cerebromuscular dystrophies, such as the syndromes of: Walter-Warburg, Fukuyama and type 1 and 2 pontocerebellar hypoplasia, which are diseases autosomal recessive neurodegeneratives.

In pontocerebelar hypoplasias, respiratory abnormalities and cerebellar are signs of frequent manifestation. They involve neuronal degeneration of the anterior horn of the spinal cord, causing spinal muscular atrophy type I, with significant feeding difficulties and severe hypotonia.

The classification of cerebellar malformations, are often related to partial agenesis and dysplasia:

Predominant agenesis with or without dysplasia associated with

  1. Vermis:
    1. With cyst: Dandy Walker syndrome (SDW).
    2. Without cyst: Joubert syndrome (SJ).
  2. Hemispheres

Predominant dysplasia

  • Vermis: Rhombencephalo-synapse (RES).
  • Vermis +/- hemispheres
  • Congenital muscular dystrophies
  • Walter Warburg syndrome (WWS)
  • Lhermitte-Duclos syndrome (LDD)
  • Isolated.

Cerebellar verm hypoplasia (small cerebellum)

  1. With cyst: Dandy Walker syndrome.
  2. Without cyst:
    1. With bridge hypoplasia of diverse etiology.
    2. With hypoplasia of the bridge and hemispheres.
      1. Pontoneocerebellar hypoplasia (Barth Type 1 and 2).

Atrophy: vermis +/- cerebral hemispheres

  • Evolutionary or progressive: Metabolic disease.
  • Static: Posttraumatic mental retardation.

Phenocerebellar hypoplasia (HPC) phenotypes

The severe cognitive and motor retardation, are characteristics present in the subtypes of pontocerebelar hypoplasia (HPC), depending on the affected gene may have various clinical manifestations:

Type of Pontocerebellar Hypoplasia Associated GenesPhenotype


Spinal muscular atrophy

with hypoplasia







Spinal cord involvement. It causes clinical signs that include: central and peripheral motor dysfunctions, congenital contractures, degeneration of the anterior horn of the cord, muscular atrophy, suction problems and respiratory failure. The prevalence is <1 / 1 000 000, It is a phenotype considered lethal.

1 B


Related to a change of sense (missense) type mutation in homozygosis in exon 1 of the EXOSC-3 gene, this gene encodes a component of the exosome, a multiprheoretic complex involved in RNA processing.

It usually begins when the baby is born, it is characterized by the degeneration of the motor neurons of the brain and spine, which cause decreased body tone, respiratory failure, muscular atrophy, progressive microcephaly and delayed global development.

1 C


With severe neurodegenerative disorder, it is autosomal recessive. It is characterized by severe muscle weakness and developmental problems evident in the first months of life. Affected infants show delayed psychomotor development, often with visual and hearing impairment, can die from respiratory failure. Brain images usually show cerebellar hypoplasia, hypoplasia of the corpus callosum and immature myelination.
1 dEXOSC9Show similarities with HPC 1C.

Volendam neurodegenerative disease.


With dyskinetic movements and seizures.

HPC 2BTSEN2Progressive microcephaly from birth, with epilepsy, extrapyramidal dyskinesia and chorea, dystonia, visual problems and swallowing difficulties.





Cerebral and cerebellar atrophy progressive



Selenocysteine ​​synthase

Cerebral and cerebellar atrophy, seizures, irritability, ataxia and extreme spasticity.
HPC 2EVPS53Deep mental retardation, progressive microcephaly, spasticity and early onset epilepsy.



Variable neurological signs and symptoms, cognitive and motor retardation, speech difficulties or inability, seizures and spasticity.

Cerebellar atrophy with progressive microcephaly.



Severe developmental delay accompanied by progressive microcephaly, seizures, short stature and optic atrophy.



Severe HPC2 of prenatal origin, have excess fluid in the amniotic sac, muscle contractures, involuntary muscle contractions, breathing difficulties and cortical hypoplasia.

It is characterized by a severe course and early lethality (Budde et al., 2008), usually have a premature death after birth.


Olivopontocerebellar hypoplasia of fetal initiation



Severe prenatal HPC2 of early onset with intrauterine crises, autosomal recessive inheritance.



Severe encephalopathy in the newborn with hypotonia, seizures, edema, increased levels of blood lactate and mitochondrial respiratory chain defects.



Hypotonia, apneic episodes and seizures.

Genital abnormalities, sex reversal, there may be presence of testicular development in the absence of Y chromosome, embryonic testicular regression syndrome (ETRS) or faded testis syndrome.



Non-progressive HPC with severe psychomotor retardation, abnormal movements, hypotonia, spasticity and visual problems.
HPC 9 AMPD2Delayed severe psychomotor development with progressive microcephaly, spasticity, seizures and brain abnormalities, including cerebral atrophy, thin corpus callosum and delayed myelination.

HPC 10


HPC 11


Delay in severe psychomotor development with intellectual disability and speech difficulties, microcephaly, dysmorphic characteristics and pontocerebellar hypoplasia in neuroimaging.

HPC 12


Pontocerebellar hypoplasia of prenatal onset, microcephaly and arthrogryposis. Neurodegeneration with iron accumulation in the brain.

Eggens et al. (2014), according to different criteria, classified the following clinical manifestations of type 1 B pontocerebelar hypoplasia, associated with the EXOSC3 gene:

You may be interested: Hydrocephalus, a hydrodynamic disorder of the cerebrospinal fluid

Cerebellar hypoplasia and some associated syndromes

As can be seen, each subtype of cerebellar hypoplasia can have different clinical manifestations, since they are rare diseases, they are still an important object of study for neurosciences and genetics.

Cerebellar hypoplasia (HC), may occur linked to other conditions, the most frequent are hemiagenesis, total or vermis agenesis, and neurological syndromes such as:

  1. Dandy-Walker syndrome (SDW): the heterozygous loss of the ZIC1 and ZIC4 genes is involved in the malformation of the syndrome.
  2. Arnold-Chiari malformation type 2 and 4: in the last one, lack of development in cerebellar structures, part of the cerebellum located below the foramen, constituted by isolated hypoplasia of the cerebellum, may be a variant of SDW.
  3. Werdinig-Hoffman syndrome: It is an autosomal disease, neuromuscular and degenerative character implies spinal muscular atrophy (SMA), although it occurs infrequently, in most cases it turns out to be fatal.
  4. Walker-Warburg syndrome: congenital muscular dystrophy that involves abnormalities in the eyes, brain and cerebellum.
  5. Congenital disorder of glycosylation of type 1A proteins.
  6. Norman syndrome: ataxia and mental retardation.
  8. COACH syndrome: cerebellar hypoplasia, oligophrenia, congenital ataxia, coloboma and hepatopathy.
  9. Cerebellar anomaly-Gillespie aniridia.
  10. Barth syndrome: Pontocerebellar hypoplasia.

The OPHN1 syndrome, is another subtype of cerebral hypoplasia, also known as oligophrenin 1 syndrome, is a very rare disease among the population, transmitted by dominant inheritance linked to the X chromosome, it is a rare syndromic form of cerebellar dysgenesis characterized by an intellectual deficit of degree Moderate to severe, hypotonia, inability to coordinate movements, developmental delay, abnormal behavior, underdeveloped genitals, strabismus and characteristic facial features.

Cerebellar hypoplasia: Diagnosis and treatment

The clinical diagnosis is validated by several high resolution neuroimaging of the brain and specific cerebellar areas, some of the studies that are often performed are computed tomography or magnetic resonance imaging (MRI), it can be fetal even, they help differentiate the acquisition of anatomical information, in them, you can see gray substance and white substance axial imaging is used to evaluate the microstructural integrity of white matter. In some cases, angiographic studies, ventriculomegaly and / or genetic studies are requested.

The optimal treatment is multidisciplinary focused on reducing the symptoms, therefore depends on the severity of the clinical manifestations and the underlying disorders. In the case of patients who have balance problems, they can find great support in the rehabilitation therapies specialized for balance and coordination.

The advantages of the therapeutic process are valuable, they serve as an important support for the person with cerebral hypoplasia and their family, it is necessary that there be assertive communication for adequate conflict management, as well as assignments for the different responsibilities as relatives of a person with cerebellar hypoplasia. It is recommended that the family take at least one psychotherapeutic process and constantly inform about HC through different means and different health professionals.

It is necessary to elaborate with knowledge what it means to have such a loved one, so different and so unique ... Knowing more about the condition, can provide the best possible guidelines to the relatives of patients with HC, making it possible to better adapt to their individuals circumstances finally love builds and strengthens, can help transcend many barriers and obstacles that arise in their processes and their path.


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  2. Human Phenotype Ontology (HPO)
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Other references

  1. Cruz-Hernández, Manuel et al. (2007). Treaty of Pediatrics. New edition. Volume 1 and 2. Ocean: Barcelona, ​​Spain.
  2. Barth, P. G. Pontocerebellar hypoplasias: an overview of a group of inherited neurodegenerative disorders with fetal onset. Brain Dev. 15: 411-422, 1993.
  3. Eggens VRC, Barth PG, Baas F. EXOSC3-Related Pontocerebellar Hypoplasia. 2014. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Armemiya A, Bean LJH, et al., Editors. GeneReview. Seattle (WA): University of Washington, Seattle; 1993-2016.
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