Dysgenesis of the Posterior Fossa: Syndrome Associated and Clinical Manifestations
Posterior Fossa Dysgenesis
The classification of disorders of the development of the cranial nerve, brainstem, and cerebellum remains anatomic, but future classification systems will likely be based on the molecular biology of brain development based on the genes involved and the roles they play in orchestrating brain architecture.
Congenital Cranial Dys-innervation Disorders
Absence of the cranial nerves or the corresponding central nuclei has been described in several conditions and includes optic nerve defects, congenital ptosis, Marcus Gunn phenomenon (sucking jaw movements causing simultaneous eyelid blinking; this congenital synkinesis results from abnormal innervation of the trigeminal and oculomotor nerves), defects of the trigeminal and auditory nerves, and defects of cranial nerves IX, X, XI, and XII. Increased understanding of these disorders and their genetic causes has led to the term congenital cranial dysinnervation disorders.
Optic nerve hypoplasia
can occur in isolation or as part of the septooptic dysplasia complex (de Morsier syndrome). Septooptic dysplasia can be caused by a mutation in the HESX1 gene. Möbius syndrome is characterized by bilateral facial weakness, which is often associated with paralysis of the abducens nerve. Hypoplasia or agenesis of brainstem nuclei, as well as absent or decreased numbers of muscle fibers, has been reported. Affected infants present in the newborn period with facial weakness, causing feeding difficulties owing to a poor suck. The immobile, dull facies might give the incorrect impression of intellectual impairment; the prognosis for normal development is excellent in most cases. The facial appearance of Möbius syndrome has been improved by facial surgery.Duane retraction syndrome
characterized by congenital limitation of horizontal globe movement and some globe retraction on attempted adduction and is believed to be the result of abnormal innervation by the oculomotor nerve to the lateral rectus muscle. Abnormalities of cranial nerve development have been demonstrated in this condition. Less common than Duane retraction syndrome and Möbius syndrome are the group of disorders known as congenital fibrosis of the extraocular muscles. Congenital fibrosis of the extraocular muscles is characterized by severe restriction of eye movements and ptosis from abnormal oculomotor and trochlear nerve development and/or from abnormalities of extraocular muscle innervation.Brainstem and Cerebellar Disorders
Disorders of the posterior fossa structures include abnormalities not only of the brainstem and cerebellum, but also of the CSF spaces.
Commonly encountered malformations include Chiari malformation, Dandy-Walker malformation, arachnoid cysts, mega cisterna magna, persisting Blake pouch, Joubert syndrome, rhombencephalosynapsis, Lhermitte-Duclos disease, and the pontocerebellar hypoplasias.
Chiari malformation
the most common malformation of the posterior fossa and hindbrain. It consists of herniation of the cerebellar tonsils though the foramen magnum. Often, there is also an associated developmental abnormality of the bones of the skull base leading to a small posterior fossa. Cases can be either asymptomatic or symptomatic. Chiari malformations may be isolated or seen in patients with Ehlers-Danlos syndrome, cystinosis, or other bone of connected tissue disorders. When symptoms develop, they often do not do so until late childhood. Symptoms include headaches that are worse with straining and other maneuvers that increase intracranial pressure. Symptoms of brainstem compression such as diplopia, oropharyngeal dysfunction, spasticity, tinnitus, and vertigo can occur. Obstructive hydrocephalus and/or syringomyelia can also occur.Dandy-Walker malformation
part of a continuum of posterior fossa anomalies that include cystic dilation of the fourth ventricle, hypoplasia of the cerebellar vermis, hydrocephalus, and an enlarged posterior fossa with elevation of the lateral venous sinuses and the tentorium. Extracranial anomalies are also seen. Variable degrees of neurologic impairment are usually present. The etiology of Dandy-Walker malformation includes chromosomal abnormalities, single gene disorders, and exposure to teratogens.Arachnoid cysts of the posterior fossa
can be associated with hydrocephalus. Mega cisterna magna is characterized by an enlarged CSF space inferior and dorsal to the cerebellar vermis and when present in isolation may be considered a normal variant. Persisting Blake pouch is a cyst that obstructs the subarachnoid space and is associated with hydrocephalus.Joubert syndrome
an autosomal recessive disorder (ciliopathy) with significant genetic heterogeneity that is associated with cerebellar vermis hypoplasia and the pontomesencephalic molar tooth sign (a deepening of the interpeduncular fossa with thick and straight superior cerebellar peduncles). It is associated with hypotonia, ataxia (as toddler), characteristic breathing abnormalities including episodic apnea and hyperpnea (which improves with age), global developmental delay, nystagmus, strabismus, ptosis, and oculomotor apraxia. There can be many associated systemic features (Joubert syndrome and related disorders), including progressive retinal dysplasia (Leber congenital amaurosis), coloboma, congenital heart disease, microcystic kidney disease, liver fibrosis, polydactyly, tongue protrusion, and soft tissue tumors of the tongue.Rhombencephalosynapsis
It is an absent or small vermis associated with a nonseparation or fusion of the deep midline cerebellar structures. Ventriculomegaly or hydrocephalus is often seen. There is a variable clinical presentation from normal function to cognitive and language impairments, epilepsy, and spasticity. Lhermitte-Duclos disease is a dysplastic gangliocytoma of the cerebellum leading to focal enlargement of the cerebellum and macrocephaly, cerebellar signs, and seizures.Pontocerebellar hypoplasias
a group of disorders characterized by impairment of cerebellar and pontine development together with histopathologic features of neuronal death and glial replacement. Clinical features tend to be nonspecific and include hypotonia, feeding difficulties, developmental delay, and breathing difficulties.Classification
type I (with features of anterior horn cell involvement), type II (with extrapyramidal features, seizures, and acquired microcephaly),Associations and Causes Include
Walker-Warburg syndrome, muscle–eye–brain disease Congenital disorders of glycosylation type 1A Mitochondrial cytopathies Teratogen exposure Congenital cytomegalovirus infection 3-methylglutaconic aciduria PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy) Autosomal recessive cerebellar hypoplasia in the Hutterite population Lissencephaly with cerebellar hypoplasia Other subtypes of pontocerebellar hypoplasia.Dysgenesis of the Posterior Fossa
- What is the primary anatomical region affected in dysgenesis of the posterior fossa?
Answer: The cerebellum and surrounding structures in the posterior cranial fossa - Which of the following is NOT a common subtype of posterior fossa dysgenesis?
Answer: Cerebellar agenesis - What is the most common form of posterior fossa dysgenesis?
Answer: Dandy-Walker malformation - In Dandy-Walker malformation, which of the following structures is typically absent or underdeveloped?
Answer: The cerebellar vermis - What imaging modality is considered the gold standard for diagnosing posterior fossa dysgenesis?
Answer: Magnetic Resonance Imaging (MRI) - Which of the following is a characteristic feature of Joubert syndrome?
Answer: The "molar tooth sign" on axial MRI - What is the term for the partial or complete absence of the cerebellar vermis?
Answer: Rhombencephalosynapsis - Which embryonic structure gives rise to the cerebellum?
Answer: The rhombencephalon - What is the approximate gestational age at which posterior fossa malformations can typically be detected on prenatal ultrasound?
Answer: 18-20 weeks - Which of the following is NOT a typical clinical manifestation of posterior fossa dysgenesis?
Answer: Increased intracranial pressure - What is the term for the upward displacement of cerebellar tonsils through the foramen magnum?
Answer: Chiari malformation - In which type of Chiari malformation is the cerebellum and brainstem herniated into the upper cervical spinal canal?
Answer: Chiari II malformation - What genetic syndrome is associated with an increased risk of Dandy-Walker malformation?
Answer: Trisomy 18 (Edwards syndrome) - Which of the following is a common associated finding in patients with posterior fossa dysgenesis?
Answer: Hydrocephalus - What is the term for the absence or severe hypoplasia of the cerebellar hemispheres?
Answer: Cerebellar hypoplasia - Which cranial nerve nuclei are typically affected in Möbius syndrome, a condition sometimes associated with posterior fossa dysgenesis?
Answer: Abducens (CN VI) and facial (CN VII) nerve nuclei - What is the primary function of the cerebellum?
Answer: Coordination of movement and balance - Which of the following is NOT a typical symptom of cerebellar dysfunction?
Answer: Aphasia - What is the term for rhythmic, involuntary eye movements often seen in patients with cerebellar disorders?
Answer: Nystagmus - In pontocerebellar hypoplasia, which part of the brainstem is primarily affected along with the cerebellum?
Answer: The pons - What is the name of the fluid-filled space that is abnormally enlarged in Dandy-Walker malformation?
Answer: The fourth ventricle - Which of the following is a common treatment approach for hydrocephalus associated with posterior fossa dysgenesis?
Answer: Ventriculoperitoneal shunt placement - What is the term for the underdevelopment of the cerebellar vermis and corpus callosum, often associated with intellectual disability?
Answer: Aicardi syndrome - Which of the following is NOT a typical feature of Walker-Warburg syndrome?
Answer: Cerebellar hypertrophy - What is the most common chromosomal abnormality associated with Dandy-Walker malformation?
Answer: Trisomy 18 - Which of the following is a characteristic feature of rhombencephalosynapsis?
Answer: Fusion of the cerebellar hemispheres - What is the term for the absence of the cerebellar vermis with a midline connection of the cerebellar hemispheres?
Answer: Rhombencephalosynapsis - Which of the following is NOT typically associated with Joubert syndrome?
Answer: Macrocephaly - What is the primary embryological process disrupted in posterior fossa dysgenesis?
Answer: Hindbrain development - Which of the following conditions is characterized by hypoplasia of the cerebellar vermis and elongation of the superior cerebellar peduncles?
Answer: Joubert syndrome
