Proteus syndrome associated with hemimegalencephaly and Ohtahara syndrome: Report of two cases

Bastos, Halisson; Silva, Paula Fabiana Sobral da; Albuquerque, Marco Antônio Veloso; Mattos, Adriana; Riesgo, Rudimar dos Santos; Ohlweiler, Lygia; Winckler, María Isabel Bragatti; Bragatti, José Augusto; Duarte, Rodrigo Dias; Zandoná, Denise Isabel

doi:10.1016/j.seizure.2007.11.001

Cited by 17 publications

(13 citation statements)

References 21 publications

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“…TSC1 and TSC2 dimers inhibit mTORC1 activity, but when mutations impair their function, diseases such as TSC or CDIIB ensue (Curatolo et al., 2001; Becker et al., 2002; Schonberger et al., 2009; Crino, 2011). Other disorders with overactivated mTORC1 include PMSE (mutations of STRADalpha ) (Puffenberger et al., 2007; Orlova et al., 2010) and PTENopathies (Cowden syndrome, Bannayan‐Riley‐Ruvalcaba syndrome and Proteus syndrome) where loss of function mutation of PTEN are seen (Cross, 2005; Bastos et al., 2008; Pilarski et al., 2011). Neurofibromatosis type 1, which is due to neurofibromin 1 ( NF1 ) mutations, may also lead to overactivation of the mTOR pathway (Motte et al., 1993; Ruggieri et al., 2009).…”

Section: Genetic Dysregulation Of the Mtor Pathway Associated With Ementioning

confidence: 99%

Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target

Galanopoulou¹,

Gorter²,

Cepeda³

2012

Epilepsia

144

105

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Summary The mTOR signaling pathway regulates cell growth, differentiation, proliferation and metabolism. Loss of function mutations in upstream regulators of mTOR have been highly associated with dysplasias, epilepsy and neurodevelopmental disorders. These include tuberous sclerosis, which is due to mutations in TSC1 or TSC2 genes, mutations in phosphatase and tensin homolog (PTEN) as in Cowden syndrome, polyhydramnios, megalencephaly, symptomatic epilepsy syndrome (PMSE) due to mutations in the STE20-related kinase adaptor alpha (STRADalpha), and neurofibromatosis type 1 attributed to neurofibromin 1 mutations. Inhibition of the mTOR pathway with rapamycin may prevent epilepsy and improve the underlying pathology in mouse models with disrupted mTOR signaling, due to PTEN or TSC mutations. However the timing and duration of its administration appear critical in defining the seizure and pathology-related outcomes. Rapamycin application in human cortical slices from patients with cortical dysplasias reduces the 4-aminopyridine induced oscillations. In the multiple-hit model of infantile spasms, pulse high dose rapamycin administration can reduce the cortical overactivation of the mTOR pathway, suppresses spasms and has disease-modifying effects by partially improving cognitive deficits. In post-status epilepticus models of temporal lobe epilepsy, rapamycin may ameliorate the development of epilepsy-related pathology and reduce the expression of spontaneous seizures, but its effects depend on the timing and duration of administration, and possibly the model used. The observed recurrence of seizures and epilepsy-related pathology after rapamycin discontinuation suggests the need for continuous administration to maintain the benefit. However, the use of pulse administration protocols may be useful in certain age-specific epilepsy syndromes, like infantile spasms, whereas repetitive pulse rapamycin protocols may suffice to sustain a long-term benefit in genetic disorders of the mTOR pathway. In summary, mTOR dysregulation has been implicated in several genetic and acquired forms of epileptogenesis. The use of mTOR inhibitors can reverse some of these epileptogenic processes although their effects depend upon the timing and dose of administration as well as the model used.

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Section: Genetic Dysregulation Of the Mtor Pathway Associated With Ementioning

confidence: 99%

Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target

Galanopoulou¹,

Gorter²,

Cepeda³

2012

Epilepsia

144

105

View full text Add to dashboard Cite

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“…[8910] Intellectual disability and seizures may be the presenting features in these individuals and such individuals may have associated distinct facial features. [11] In our case, epilepsy and hemimegalencephaly were noted.…”

Section: Discussionmentioning

confidence: 99%

Proteus syndrome with neurological manifestations: A rare presentation

et al. 2017

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Proteus syndrome (PS) is an extremely rare and complex disorder. Approximately 200 cases have been reported, and it seems to affect people of all ethnic and racial groups. PS is characterized by segmental overgrowth of multiple tissues and organs including vascular malformations, lipomatous overgrowth, hyperpigmentation, and various types of nevi. We hereby present a 7-year-old boy who presented with seizures and overgrowth of one-half of the body. Although classical physical features have been described, epilepsy and other neurological manifestations are rarely reported features of PS. Early detection of association of epilepsy and hemimegalencephaly with PS can prevent/minimize the neurological complications, disability, morbidity, and mortality.

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“…Three from Category C have been reported and are mentioned in the review. Interestingly, the occurrence of neurological deficits preceded overgrowth manifestations in three cases [1,15,16].…”

Section: Neurological Manifestationsmentioning

confidence: 99%

“…There are two reported cases of triple association of Ohtahara syndrome, hemimegalencephaly (HME) and Proteus syndrome [15]. In the majority of patients with Proteus syndrome seizures were treated by multiple anticonvulsants with poor control.…”

Section: Seizuresmentioning

confidence: 99%