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Zpráva o onemocněních · Neurological

MTOR Pathway Megalencephaly and Overgrowth Disorders

Whole genome sequencing reads five growth pathway genes, AKT3, MTOR, PIK3CA, PIK3R2 and CCND2, for changes that can cause an enlarged brain, brain folding differences and sometimes body overgrowth.

Zpráva o onemocněních hledá vzácné varianty, o nichž je známo, že způsobují onemocnění, na něž se zpráva zaměřuje.

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O tomto condition

A group of conditions in which overactivity of a cell growth pathway causes a large brain, brain malformations and sometimes body overgrowth. This report analyses the AKT3, MTOR, PIK3CA, PIK3R2 and CCND2 genes.

This is a group of conditions in which overactivity of the PI3K-AKT-MTOR growth pathway causes a large brain, malformations of the brain's folds and sometimes overgrowth of the body. Features often include developmental delay and epilepsy. Hydrocephalus, a build-up of fluid in the brain, can also occur, and extra fingers or toes are seen in some people.

The conditions are caused by changes in AKT3, MTOR, PIK3CA, PIK3R2 or CCND2, which are genes of this pathway. Most cases arise new in one copy of the gene, and some changes arise after conception so that only some cells are affected, a pattern called mosaicism. The report notes that low-level mosaicism may not be detected in a blood sample, so a negative result does not rule out the condition.

Care involves brain imaging to monitor for hydrocephalus, epilepsy treatment, which sometimes includes surgery, and developmental support. Alpelisib is approved for reducing overgrowth in PIK3CA-related overgrowth, but it is not known whether it helps the brain features. Genetic counselling is recommended.

Všech 2 onemocnění, která analyzujeme

Overgrowth and Cerebral Malformations due to MTOR Pathway Gene Changes

Caused by activating changes in AKT3, MTOR, PIK3CA or PIK3R2, genes of the PI3K-AKT-MTOR growth pathway. Changes either arise de novo in one copy of the gene in every cell, or after conception so that only some cells are affected (mosaicism).

Příznaky a projevy

A large head (megalencephaly) or one enlarged brain hemisphere, often with polymicrogyria or focal cortical dysplasia, developmental delay and epilepsy. PIK3CA-related forms can also cause asymmetric overgrowth of the body and vascular malformations. Hydrocephalus and extra fingers can also occur.

Co se diagnózou změní

Care involves brain imaging and monitoring for hydrocephalus, epilepsy treatment, which sometimes includes surgery, and developmental support. Alpelisib is approved for reducing overgrowth in PIK3CA-related overgrowth, but it is not known whether it helps the brain features. Most cases arise new, so recurrence risk is usually low, but genetic counselling is recommended.

Analyzované geny

Zahrnuty jsou také specifické formy

  • Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 3 (CCND2)

    Autozomálně dominantní

    Caused by a change in one copy of CCND2, which encodes cyclin D2, a protein that controls cell division and growth. Changes usually arise de novo.

    CCND2

Zahrnuje 15 příbuzných podtypů ↓
  • hemimegalencephaly
  • isolated focal cortical dysplasia
  • isolated focal cortical dysplasia type I
  • isolated focal cortical dysplasia type Ia
  • isolated focal cortical dysplasia type Ib
  • isolated focal cortical dysplasia type Ic
  • isolated focal cortical dysplasia type II
  • isolated focal cortical dysplasia type IIa
  • isolated focal cortical dysplasia type IIb
  • macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
  • megalencephaly-capillary malformation-polymicrogyria syndrome
  • megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
  • megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2
  • megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3
  • megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
MONDO:0100283Zdroje: [1][2][3][4]

Proč sekvenování celého genomu

Several genes in one growth pathway can cause these conditions, and this report analyses five of them. Most cases arise new, so the risk to future children is usually low.

Different genes can cause similar features

Changes in AKT3, MTOR, PIK3CA, PIK3R2 or CCND2 can each cause a condition in this group, and whole genome sequencing reads all five in the same test. Several of these genes give similar brain features, which is why they are read together.

Epilepsy and brain imaging need follow-up

Regular neurology follow-up monitors and treats epilepsy, and brain MRI is used to watch for hydrocephalus. Developmental support is recommended because developmental delay is common in this group.

Omezení

  • Some of these conditions are caused by mosaic changes present in only some cells, and sometimes only in the brain or affected tissue. Low-level mosaicism may not be detected in a blood sample, so a negative result does not rule out the condition.

Reference

  1. Mirzaa G, 2016. MPPH Syndrome. GeneReviews
  2. Mirzaa G, Graham JM, Keppler-Noreuil K, 2013. PIK3CA-Related Overgrowth Spectrum. GeneReviews
  3. Rivière JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL et al., 2012. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nature genetics
  4. Gerasimenko A, Baldassari S, Baulac S, 2023. mTOR pathway: Insights into an established pathway for brain mosaicism in epilepsy. Neurobiology of disease
  5. CCND2 gene. MedlinePlus Genetics

Další neurological conditions

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