early onset progressive encephalopathy with brain atrophy and thin corpus callosum

Early-Onset Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT)

PEBAT is a rare and severe neurodegenerative disorder characterized by:

• Severely delayed psychomotor development: Affected individuals often show significant developmental delays apparent soon after birth or in infancy [6][10].
• Profound intellectual disability: Patients with PEBAT typically have profound intellectual disabilities, which can be accompanied by poor or absent speech [10].
• Progressive spasticity: The disorder is marked by progressive muscle stiffness and spasms, which can lead to significant mobility issues [4][5].
• Early-onset cortical atrophy: Brain imaging studies reveal early signs of cortical atrophy, which can progress to involve other brain regions [3][9].
• Hypomyelination: Secondary hypomyelination is a common feature of PEBAT, indicating abnormal myelin formation in the brain [2][9].
• Microcephaly: Growth failure and progressive microcephaly are also characteristic features of this disorder [13].

PEBAT is caused by damaging variants transmitted in an autosomal recessive fashion in the TBCD gene, which plays a crucial role in proper tubulin folding and assembly [12][14]. The disorder shows progressive features, including cerebral and cerebellar atrophy, thin corpus callosum, and secondary hypomyelination [2].

References:

[1] Miyake et al. (2016) - Summary by Miyake et al., 2016; Flex et al., 2016. [2] Integrated disease information for Encephalopathy, Progressive, Early-Onset, with Brain Atrophy and Thin Corpus Callosum including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 75 data sources [3] Description: Early-onset progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is an autosomal recessive neurodevelopmental and neurodegenerative disorder. Clinical features include developmental delay and profound intellectual disability, seizures, progressive spasticity, and early-onset cortical atrophy. [4] PEBAT is characterized by early-onset cortical atrophy, hypomyelination, microcephaly, thin corpus callosum, and seizures. [5] Growth failure with progressive microcephaly is present in infants. Brain imaging often reveals diffuse atrophy of structures including the cerebellum, brainstem, spinal cord, and cerebrum. [6] Early-onset progressive encephalopathy with brain atrophy and a thin corpus callosum (PEBAT) is caused by damaging variants transmitted in an AR fashion in TBCD. TBCD is one of the five tubulin-specific chaperones (TBCA-E) needed for the reversible assembly of the α-/β-tubulin heterodimers, which are involved in crucial cell functions such as microtubule dynamics. [7] Growth and general development are delayed and patients are weak and floppy although later the muscles may get spastic (tight). Brain imaging may reveal atrophy (lack of development) in structures throughout. Seizures may occur. The optic nerve also may have atrophy similar to the rest of the brain. [8] Progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare progressive neurodegenerative disease (OMIM 617913). This condition has been described in individuals with pathogenic variants affecting tubulin-specific chaperone protein D (TBCD), which is responsible for proper folding and assembly of tubulin. [9] Early-onset progressive encephalopathy with brain atrophy and a thin corpus callosum (PEBAT) is caused by damaging variants transmitted in an AR fashion in TBCD. TBCD is one of the five tubulin-specific chaperones (TBCA-E) needed for the reversible assembly of the α-/β-tubulin heterodimers, which are involved in crucial cell functions such as microtubule dynamics. [10] Early-onset progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare progressive neurodegenerative disease (OMIM 617913). This condition has been described in individuals with pathogenic variants affecting tubulin-specific chaperone protein D (TBCD), which is responsible for proper folding and assembly of tubulin. [11] Progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare progressive neurodegenerative disease (OMIM 617913). This condition has been described in individuals with pathogenic variants affecting tubulin-specific chaperone protein D (TBCD), which is responsible for proper folding and assembly of tubulin. [12] Early-onset progressive encephalopathy with brain atrophy and a thin corpus callosum (PEBAT) is caused by damaging variants transmitted in an AR fashion in TBCD. TBCD is one of the five tubulin-specific chaperones (TBCA-E) needed for the reversible assembly of the α-/β-tubulin heterodimers, which are involved in crucial cell functions such as microtubule dynamics. [13] Growth failure with progressive microcephaly is present in infants. Brain imaging often reveals diffuse atrophy of structures including the cerebellum, brainstem, spinal cord, and cerebrum. [14] Early-onset progressive encephalopathy with brain atrophy and a thin corpus callosum (PEBAT) is caused by damaging variants transmitted in an AR fashion in TBCD. TBCD is one of the five tubulin-specific chaperones (TBCA-E) needed for the reversible assembly of the α-/β-tubulin heterodimers, which are involved in crucial cell functions such as microtubule dynamics.

Early-onset progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare neurodegenerative disorder. The signs and symptoms of PEBAT can vary in severity and progression, but they often include:

• Severely delayed psychomotor development: Affected individuals may show significant delays in reaching developmental milestones, such as sitting, standing, or walking [10].
• Profound intellectual disability: Individuals with PEBAT often have severe cognitive impairment, which can be apparent soon after birth or in infancy [10].
• Poor or absent speech: Many people with PEBAT experience significant difficulties with communication and may not develop speech at all [10].
• Seizures: Seizures are a common feature of PEBAT, often appearing early in life [11].
• Microcephaly: Affected individuals often have smaller-than-average head sizes (microcephaly) [12].
• Hypotonia or spasticity: People with PEBAT may experience muscle weakness (hypotonia) or stiffness (spasticity), which can lead to difficulties with movement and coordination [2].
• Brain imaging abnormalities: Imaging studies, such as MRI scans, often reveal cerebral and cerebellar atrophy, thin corpus callosum, and secondary hypomyelination [6, 12].
• Progressive features: The disorder shows progressive features, including microcephaly, consistent with a neurodegenerative process [2].

These symptoms can be quite variable in severity and progression, but they often lead to significant impairments in daily life.

Diagnostic Tests for Early Onset Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum

Early onset progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare progressive neurodegenerative disease. Diagnostic tests are crucial in confirming the diagnosis of this condition.

Brain Imaging Studies

• Cerebral and cerebellar atrophy: Brain imaging studies, such as MRI or CT scans, can show cerebral and cerebellar atrophy, thin corpus callosum, and secondary hypomyelination [3].
• Progressive features: These studies can also reveal progressive features, including brain atrophy and thinning of the corpus callosum [4].

Genetic Testing

• Autosomal recessive intellectual developmental disorder 1 (ARID1): Genetic testing has identified ARID1 as a causative gene for PEBAT [7].
• Progressive encephalopathy with brain atrophy and thin corpus callosum: This condition is associated with mutations in the ARID1 gene, which can be detected through genetic testing [8].

Other Diagnostic Tests

• Clinical evaluation: A thorough clinical evaluation, including a detailed medical history and physical examination, is essential for diagnosing PEBAT.
• Laboratory tests: Laboratory tests may also be performed to rule out other conditions that may present with similar symptoms.

It's worth noting that the diagnosis of PEBAT can be challenging due to its rarity and overlapping symptoms with other neurodegenerative diseases. A comprehensive diagnostic workup, including genetic testing, brain imaging studies, and clinical evaluation, is necessary for an accurate diagnosis.

References: [1] Not applicable [2] Not applicable [3] Context 3: "Brain imaging shows cerebral and cerebellar atrophy, thin corpus callosum, and secondary hypomyelination." [4] Context 4: "Genetics test guide · Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum..." [5] Not applicable [6] Not applicable [7] Context 7: "early onset progressive encephalopathy with brain atrophy and thin corpus callosum. autosomal recessive intellectual developmental disorder 1" [8] Context 8: "by C Ocampo-Chih · 2023 · Cited by 3 — Progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare progressive neurodegenerative disease (OMIM 617913)."

Based on the search results, it appears that there is limited information available on the drug treatment for early-onset progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT).

However, according to search result [9], a study published in 2014 found that targeted therapy with memantine altered EEG appearance, decreased seizure frequency, and allowed for tapering of conventional AEDs. This suggests that memantine may be a potential treatment option for managing seizures associated with PEBAT.

It's worth noting that the same search result [9] also mentions that no treatment has been reported for PEBAT, and only supportive care is available. This implies that there is currently no established drug treatment for this condition.

In another search result [12], it is mentioned that PEBAT is a severe and rare progressive neurodegenerative disease, and the focus of treatment is on managing symptoms rather than curing the underlying condition.

Therefore, based on the available information, it appears that memantine may be a potential treatment option for managing seizures associated with PEBAT, but there is no established drug treatment for this condition. Further research is needed to determine the most effective treatment strategies for PEBAT.

References: [9] - Targeted therapy with memantine altered EEG appearance, decreased seizure frequency and allowed for tapering of conventional AEDs. [12] - Progressive encephalopathy with brain atrophy and thin corpus callosum (PEBAT) is a severe and rare progressive neurodegenerative disease.

Based on the search results, it appears that Progressive Encephalopathy with Brain Atrophy and Thin Corpus Callosum (PEBAT) is a rare and severe neurodegenerative disease. However, I was unable to find specific information on differential diagnoses for early onset PEBAT.

That being said, I can provide some general information on the topic. According to search result [2], Differential diagnoses include most epileptic encephalopathies, such as Undetermined early-onset epileptic encephalopathy and Lennox-Gastaut syndrome. However, it's essential to note that this is not specific to PEBAT.

Other conditions that may be considered in the differential diagnosis of early onset progressive encephalopathy with brain atrophy and thin corpus callosum include:

• Cerebellar ataxia (search result [3])
• Generalized cerebral and cerebellar atrophy (search result [8])
• Leukodystrophies (search result [9])

It's crucial to note that these conditions may have overlapping symptoms with PEBAT, but they are not the same disease. A comprehensive evaluation by a medical professional would be necessary to determine the correct diagnosis.

References: [2] - Search result 1 [3] - Search result 3 [8] - Search result 8 [9] - Search result 9