Materiały źródłowe

• #1 Neurofibromatosis type 2 (NF2)

  https://www.nhs.uk/conditions/neurofibromatosis-type-2/

  Neurofibromatosis type 2 (NF2) is a lifelong condition that usually gets worse over time. […] NF2 can affect how long you live, but this depends on your symptoms and how they affect you. Your care team will be able to speak to you about life expectancy if you want to know more.

• #2 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  The prognosis of neurofibromatosis type 2 (NF2) depends on a number of factors, including age of symptom onset, degree of hearing deficit, and number and location of various tumors. Although age of onset is relatively similar within families, the age range can vary from 2-70 years. While the tumors themselves are relatively indolent and do not undergo malignant transformation, studies performed in the late 1980s and early 1990s showed clearly that significant rates of mortality and morbidity are associated with the diagnosis of NF2. […] One such study suggested that the survival from the time of actual diagnosis averages 15 years; however, this may be evolving with improved diagnosis, surgical techniques, surveillance, screening, and recognition of mild disease (due in part to increased physician awareness and availability of molecular diagnostic options).

• #3 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  The prognosis of neurofibromatosis type 2 (NF2) depends on a number of factors, including age of symptom onset, degree of hearing deficit, and number and location of various tumors. Although age of onset is relatively similar within families, the age range can vary from 2-70 years. While the tumors themselves are relatively indolent and do not undergo malignant transformation, studies performed in the late 1980s and early 1990s showed clearly that significant rates of mortality and morbidity are associated with the diagnosis of NF2. […] One such study suggested that the survival from the time of actual diagnosis averages 15 years; however, this may be evolving with improved diagnosis, surgical techniques, surveillance, screening, and recognition of mild disease (due in part to increased physician awareness and availability of molecular diagnostic options).

• #4 Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2 in: Journal of Neurosurgery Volume 99 Issue 3 (2003) Journals

  https://thejns.org/view/journals/j-neurosurg/99/3/article-p480.xml

  Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. […] Results of a Kaplan-Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis ( 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. […] This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

• #5 Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2 – PubMed

  https://pubmed.ncbi.nlm.nih.gov/12959433/

  Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. […] Results of a Kaplan-Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. […] This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

• #6 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Neurofibromatosis type 2 (NF2) is a genetic condition marked by the development of multiple benign tumors in the nervous system. […] The survival period after diagnosis is about 15 years, and the average age at death is between 36 and 39 years, with a 10-year survival rate of 67%. […] Despite benign behavior, NF2-associated tumors result in considerable morbidity and mortality rates. […] Currently, there is no established approach to prevent or cure NF2. […] The advent of molecular biology to scheme the pathogenesis of NF2 can guide to address of new therapeutic potentials for the effective prevention and treatment of NF2-related tumors. […] Genotype-phenotype correlation and the role of NF2 genetic investigation in differentiating NF-related disorders highlight the importance of conducting genetic testing to detect at-risk patients, prognostication, and treatment.

• #7 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  The prognosis of neurofibromatosis type 2 (NF2) depends on a number of factors, including age of symptom onset, degree of hearing deficit, and number and location of various tumors. Although age of onset is relatively similar within families, the age range can vary from 2-70 years. While the tumors themselves are relatively indolent and do not undergo malignant transformation, studies performed in the late 1980s and early 1990s showed clearly that significant rates of mortality and morbidity are associated with the diagnosis of NF2. […] One such study suggested that the survival from the time of actual diagnosis averages 15 years; however, this may be evolving with improved diagnosis, surgical techniques, surveillance, screening, and recognition of mild disease (due in part to increased physician awareness and availability of molecular diagnostic options).

• #8 Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2 in: Journal of Neurosurgery Volume 99 Issue 3 (2003) Journals

  https://thejns.org/view/journals/j-neurosurg/99/3/article-p480.xml

  Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. […] Results of a Kaplan-Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis ( 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. […] This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

• #9 Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2 – PubMed

  https://pubmed.ncbi.nlm.nih.gov/12959433/

  Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. […] Results of a Kaplan-Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. […] This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

• #10 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The type and severity of NF2 manifestations depend on the type of gene mutation. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The UK NF2 Genetic Severity Score was developed to categorize the patients based on severity into severe, moderate, and mild. […] Generally, NF2 due to truncating mutations (nonsense or frameshift) is more severe and appears at younger ages. […] Patients with truncating mutations are more likely to develop symptoms earlier, have a greater risk of developing at least two CNS tumors in addition to VS, and have a shorter average life expectancy. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] The management of patients with NF2 is typically determined in a multidisciplinary setting.

• #11 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  In a more recent study of 1,192 patients with NF2, increased mortality is associated with early age at diagnosis (20 years old) and with the presence of intracranial meningiomas. […] Genetically, reduced mortality is associated with slice-site or missense mutations compared to patients with truncating mutations, and also reduced in mosaic patients compared to non-mosaic patients with NF2. […] Vestibular schwannomas are the most common and well-recognized feature of NF2 leading to significant morbidity. Symptoms of tinnitus, gradual hearing loss, and even vestibular dysfunction are frequently the initial signs of NF2. […] Although unilateral hearing loss is the most frequently presenting symptom, bilateral deafness would be expected to eventually occur in most affected individuals. […] Untreated vestibular schwannomas can extend locally and may result in brainstem compression, hydrocephalus, and, occasionally, facial nerve palsy.

• #12 Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2 in: Journal of Neurosurgery Volume 99 Issue 3 (2003) Journals

  https://thejns.org/view/journals/j-neurosurg/99/3/article-p480.xml

  Neurofibromatosis Type 2 (NF2) is an intractable disorder predisposing to multiple, recurrent tumors of the central nervous system (CNS). To clarify the survival rate and characteristics that predict poor survival, we retrospectively reviewed clinical data in cases of NF2. […] Results of a Kaplan-Meier product-limit analysis indicated that overall 5-, 10-, and 20-year patient survival rates following diagnosis of NF2 were 85, 67, and 38%, respectively. Early onset of the initial symptom significantly compromised survival; 5-, 10-, and 20-year survival rates in patients with symptom onset at an age younger than 25 years were 80, 60, and 28%, respectively, whereas in patients with symptom onset at an age of 25 years or older the rates were 100, 87, and 62%, respectively. Patients with small vestibular schwannomas at diagnosis ( 2 cm in diameter) had better rates of survival. Other variables such as sex, additional tumors in the CNS, or dermal abnormalities did not significantly affect survival. […] This first report of long-term follow-up results concerning the survival of patients with NF2 indicates an adverse effect of early symptom onset.

• #13 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  However, it is not only longevity but also the quality of life (QOL) and activities of daily living (ADL) with persisting symptoms that must be considered when considering development treatment strategies. […] By applying a combination of an NF2 mutation type/location, and age of symptom onset, we classified different degrees of functional preservation and progression, schwannoma growth rate and total interventions per year per patient. […] The periods of functional outcome preservation differed statistically significantly depending on the type of NF2 mutation. […] Truncating and Mosaic had significant effects on KPS40. […] For disabled hearing or deafness, Truncating, Splice site and Age of symptom onset25 were significant predictors. […] Our classification did not include the degree of mosaicism compared with Hallidays genetic severity score. […] This study performed genotypephenotype correlation analysis for the early prediction of functional prognosis in Japanese NF2 patients.

• #14 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The type and severity of NF2 manifestations depend on the type of gene mutation. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The UK NF2 Genetic Severity Score was developed to categorize the patients based on severity into severe, moderate, and mild. […] Generally, NF2 due to truncating mutations (nonsense or frameshift) is more severe and appears at younger ages. […] Patients with truncating mutations are more likely to develop symptoms earlier, have a greater risk of developing at least two CNS tumors in addition to VS, and have a shorter average life expectancy. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] The management of patients with NF2 is typically determined in a multidisciplinary setting.

• #15 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The type and severity of NF2 manifestations depend on the type of gene mutation. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The UK NF2 Genetic Severity Score was developed to categorize the patients based on severity into severe, moderate, and mild. […] Generally, NF2 due to truncating mutations (nonsense or frameshift) is more severe and appears at younger ages. […] Patients with truncating mutations are more likely to develop symptoms earlier, have a greater risk of developing at least two CNS tumors in addition to VS, and have a shorter average life expectancy. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] The management of patients with NF2 is typically determined in a multidisciplinary setting.

• #16 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  In a more recent study of 1,192 patients with NF2, increased mortality is associated with early age at diagnosis (20 years old) and with the presence of intracranial meningiomas. […] Genetically, reduced mortality is associated with slice-site or missense mutations compared to patients with truncating mutations, and also reduced in mosaic patients compared to non-mosaic patients with NF2. […] Vestibular schwannomas are the most common and well-recognized feature of NF2 leading to significant morbidity. Symptoms of tinnitus, gradual hearing loss, and even vestibular dysfunction are frequently the initial signs of NF2. […] Although unilateral hearing loss is the most frequently presenting symptom, bilateral deafness would be expected to eventually occur in most affected individuals. […] Untreated vestibular schwannomas can extend locally and may result in brainstem compression, hydrocephalus, and, occasionally, facial nerve palsy.

• #17 Neurofibromatosis type II – Wikipedia

  https://en.wikipedia.org/wiki/Neurofibromatosis_type_II

  Truncating mutations lead to smaller and non-functional protein products. Studies have shown that missense mutations and large deletions can both cause predominantly mild phenotypes. Phenotype is more variable in patients with splice-site mutations, and a milder disease in patients with mutations in exons 9-15. Patients with a missense mutation have a greater survival rate than nonsense and frameshift mutations.

• #18 Neurofibromatosis type II – Wikipedia

  https://en.wikipedia.org/wiki/Neurofibromatosis_type_II

  Truncating mutations lead to smaller and non-functional protein products. Studies have shown that missense mutations and large deletions can both cause predominantly mild phenotypes. Phenotype is more variable in patients with splice-site mutations, and a milder disease in patients with mutations in exons 9-15. Patients with a missense mutation have a greater survival rate than nonsense and frameshift mutations.

• #19 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The type and severity of NF2 manifestations depend on the type of gene mutation. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The UK NF2 Genetic Severity Score was developed to categorize the patients based on severity into severe, moderate, and mild. […] Generally, NF2 due to truncating mutations (nonsense or frameshift) is more severe and appears at younger ages. […] Patients with truncating mutations are more likely to develop symptoms earlier, have a greater risk of developing at least two CNS tumors in addition to VS, and have a shorter average life expectancy. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] The management of patients with NF2 is typically determined in a multidisciplinary setting.

• #20 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  However, it is not only longevity but also the quality of life (QOL) and activities of daily living (ADL) with persisting symptoms that must be considered when considering development treatment strategies. […] By applying a combination of an NF2 mutation type/location, and age of symptom onset, we classified different degrees of functional preservation and progression, schwannoma growth rate and total interventions per year per patient. […] The periods of functional outcome preservation differed statistically significantly depending on the type of NF2 mutation. […] Truncating and Mosaic had significant effects on KPS40. […] For disabled hearing or deafness, Truncating, Splice site and Age of symptom onset25 were significant predictors. […] Our classification did not include the degree of mosaicism compared with Hallidays genetic severity score. […] This study performed genotypephenotype correlation analysis for the early prediction of functional prognosis in Japanese NF2 patients.

• #21 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-022-13580-9

  We analyzed the clinical and genetic predictors of the functional disability of NF2 patients. Two types of mutations were found to act as predictors, namely Truncating and Mosaic, in addition to Age of symptom onset25. Consequently, we showed that patients of Mild had different functional prognoses compared with other NF2 patients. […] By applying a combination of an NF2 mutation type/location, and age of symptom onset, we classified different degrees of functional preservation and progression, schwannoma growth rate and total interventions per year per patient. The prediction of detailed functional outcomes can be used to plan better strategies for life-long disease management and social integration.

• #22 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #23 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-022-13580-9

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #24 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #25 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  In a more recent study of 1,192 patients with NF2, increased mortality is associated with early age at diagnosis (20 years old) and with the presence of intracranial meningiomas. […] Genetically, reduced mortality is associated with slice-site or missense mutations compared to patients with truncating mutations, and also reduced in mosaic patients compared to non-mosaic patients with NF2. […] Vestibular schwannomas are the most common and well-recognized feature of NF2 leading to significant morbidity. Symptoms of tinnitus, gradual hearing loss, and even vestibular dysfunction are frequently the initial signs of NF2. […] Although unilateral hearing loss is the most frequently presenting symptom, bilateral deafness would be expected to eventually occur in most affected individuals. […] Untreated vestibular schwannomas can extend locally and may result in brainstem compression, hydrocephalus, and, occasionally, facial nerve palsy.

• #26 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  In a more recent study of 1,192 patients with NF2, increased mortality is associated with early age at diagnosis (20 years old) and with the presence of intracranial meningiomas. […] Genetically, reduced mortality is associated with slice-site or missense mutations compared to patients with truncating mutations, and also reduced in mosaic patients compared to non-mosaic patients with NF2. […] Vestibular schwannomas are the most common and well-recognized feature of NF2 leading to significant morbidity. Symptoms of tinnitus, gradual hearing loss, and even vestibular dysfunction are frequently the initial signs of NF2. […] Although unilateral hearing loss is the most frequently presenting symptom, bilateral deafness would be expected to eventually occur in most affected individuals. […] Untreated vestibular schwannomas can extend locally and may result in brainstem compression, hydrocephalus, and, occasionally, facial nerve palsy.

• #27 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  In a more recent study of 1,192 patients with NF2, increased mortality is associated with early age at diagnosis (20 years old) and with the presence of intracranial meningiomas. […] Genetically, reduced mortality is associated with slice-site or missense mutations compared to patients with truncating mutations, and also reduced in mosaic patients compared to non-mosaic patients with NF2. […] Vestibular schwannomas are the most common and well-recognized feature of NF2 leading to significant morbidity. Symptoms of tinnitus, gradual hearing loss, and even vestibular dysfunction are frequently the initial signs of NF2. […] Although unilateral hearing loss is the most frequently presenting symptom, bilateral deafness would be expected to eventually occur in most affected individuals. […] Untreated vestibular schwannomas can extend locally and may result in brainstem compression, hydrocephalus, and, occasionally, facial nerve palsy.

• #28 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  Nonvestibular schwannomas occur in more than half of patients and are often diagnosed in patients with an earlier age at diagnosis of NF2. […] On the other hand, nonvestibular schwannomas in patients with NF2 tend to be more indolent and to grow slowly over time. This can complicate treatment decision making, since options include surgery, radiation therapy, and watchful waiting. […] Posterior subcapsular, or juvenile, cataracts can predate CNS symptomatology. These cataracts may progress over time, leading to decreased visual acuity. A fair percentage of affected individuals are found to have retinal hamartomas or epiretinal membranes that may or may not be visually significant.

• #29 Neurofibromatosis Type 2: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/1178283-overview

  Nonvestibular schwannomas occur in more than half of patients and are often diagnosed in patients with an earlier age at diagnosis of NF2. […] On the other hand, nonvestibular schwannomas in patients with NF2 tend to be more indolent and to grow slowly over time. This can complicate treatment decision making, since options include surgery, radiation therapy, and watchful waiting. […] Posterior subcapsular, or juvenile, cataracts can predate CNS symptomatology. These cataracts may progress over time, leading to decreased visual acuity. A fair percentage of affected individuals are found to have retinal hamartomas or epiretinal membranes that may or may not be visually significant.

• #30

  https://link.springer.com/article/10.1007/s00401-019-02029-5

  The occurrence of multiple meningiomas is a hallmark of NF2 and a major diagnostic criterion for the syndrome, occurring in about 50% of patients with NF2. […] NF2-associated meningiomas frequently occur at an earlier age than sporadic tumors, and presentation with meningioma in the pediatric setting should raise suspicion for NF2. […] NF2-associated ependymomas more often arise in patients with truncating NF2 mutations, suggesting that ependymomas are associated with more aggressive variants of the syndrome, as with meningiomas. […] Despite these advances, no trial-proven medical therapies have been FDA approved to date for NF2-associated schwannomas.

• #31

  https://link.springer.com/article/10.1007/s00401-019-02029-5

  The occurrence of multiple meningiomas is a hallmark of NF2 and a major diagnostic criterion for the syndrome, occurring in about 50% of patients with NF2. […] NF2-associated meningiomas frequently occur at an earlier age than sporadic tumors, and presentation with meningioma in the pediatric setting should raise suspicion for NF2. […] NF2-associated ependymomas more often arise in patients with truncating NF2 mutations, suggesting that ependymomas are associated with more aggressive variants of the syndrome, as with meningiomas. […] Despite these advances, no trial-proven medical therapies have been FDA approved to date for NF2-associated schwannomas.

• #32

  https://link.springer.com/article/10.1007/s00401-019-02029-5

  The occurrence of multiple meningiomas is a hallmark of NF2 and a major diagnostic criterion for the syndrome, occurring in about 50% of patients with NF2. […] NF2-associated meningiomas frequently occur at an earlier age than sporadic tumors, and presentation with meningioma in the pediatric setting should raise suspicion for NF2. […] NF2-associated ependymomas more often arise in patients with truncating NF2 mutations, suggesting that ependymomas are associated with more aggressive variants of the syndrome, as with meningiomas. […] Despite these advances, no trial-proven medical therapies have been FDA approved to date for NF2-associated schwannomas.

• #33 Meningiomas in patients with neurofibromatosis type 2 predominantly comprise ‘immunogenic subtype’ tumours characterised by macrophage infiltration | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01645-3

  Meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited marked immune responses by identifying myeloid cell infiltration, particularly in macrophages. […] Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.01.8 cm3/year. […] The frequency of WHO grade I meningiomas in NF2 patients tumours was 92.1% (80.9% in sporadic NF2-altered meningiomas; p=0.04). […] Our results showed that meningiomas in NF2 patients have high immune activity, as identified by identifying myeloid cell infiltration, especially by macrophages. […] The significance of the high immune activity of macrophages in meningioma tumour behaviour remains unclear. […] Our findings suggest that sporadic NF2-altered grade I meningioma mainly comprises immune-rich tumours, although some tumours are immune-poor. In contrast, meningiomas in NF2 patients predominantly comprise the immunogenic group with macrophage infiltration. […] Higher immune activity, including rich macrophages and NK T-cell activity, may contribute to the less aggressive tumour behaviour of meningiomas in NF2 patients.

• #34 Meningiomas in patients with neurofibromatosis type 2 predominantly comprise ‘immunogenic subtype’ tumours characterised by macrophage infiltration | Acta Neuropathologica Communications | Full Text

  https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-023-01645-3

  Meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited marked immune responses by identifying myeloid cell infiltration, particularly in macrophages. […] Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.01.8 cm3/year. […] The frequency of WHO grade I meningiomas in NF2 patients tumours was 92.1% (80.9% in sporadic NF2-altered meningiomas; p=0.04). […] Our results showed that meningiomas in NF2 patients have high immune activity, as identified by identifying myeloid cell infiltration, especially by macrophages. […] The significance of the high immune activity of macrophages in meningioma tumour behaviour remains unclear. […] Our findings suggest that sporadic NF2-altered grade I meningioma mainly comprises immune-rich tumours, although some tumours are immune-poor. In contrast, meningiomas in NF2 patients predominantly comprise the immunogenic group with macrophage infiltration. […] Higher immune activity, including rich macrophages and NK T-cell activity, may contribute to the less aggressive tumour behaviour of meningiomas in NF2 patients.

• #35 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #36 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-022-13580-9

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #37 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  However, it is not only longevity but also the quality of life (QOL) and activities of daily living (ADL) with persisting symptoms that must be considered when considering development treatment strategies. […] By applying a combination of an NF2 mutation type/location, and age of symptom onset, we classified different degrees of functional preservation and progression, schwannoma growth rate and total interventions per year per patient. […] The periods of functional outcome preservation differed statistically significantly depending on the type of NF2 mutation. […] Truncating and Mosaic had significant effects on KPS40. […] For disabled hearing or deafness, Truncating, Splice site and Age of symptom onset25 were significant predictors. […] Our classification did not include the degree of mosaicism compared with Hallidays genetic severity score. […] This study performed genotypephenotype correlation analysis for the early prediction of functional prognosis in Japanese NF2 patients.

• #38 Case Report: Rare Case of NF2 in Pregnancy with… | F1000Research

  https://f1000research.com/articles/11-342

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disease due to chromosome 22 (22q12.2) mutation with a prevalence of 1:33,000-40,000. As many as 50% of cases are familial, 30-60% are genetic mosaic, de novo mutations. Tumor growth in NF often becomes more rapid in pregnancy. Pregnancy with NF2 has a risk of complications of hypertension, preeclampsia, cardiovascular problems, and IUGR (Intrauterine growth restriction). […] A retrospective study in Japan showed that patients with NF2 had survival rates of 5 years, 10 years, and 20 years from diagnosis of 85%, 67%, and 38%, respectively. Pregnant women with neurofibromatosis have an increased risk of morbidity due to the progressive growth of meningiomas and schwannomas, hypertensive/cardiovascular complications, but not death during pregnancy. Additionally, pregnant women with NF2 have a high risk of developing hypertension, preeclampsia, cardiovascular problems, and Intrauterine growth restriction (IUGR).

• #39 Case Report: Rare Case of NF2 in Pregnancy with… | F1000Research

  https://f1000research.com/articles/11-342

  Neurofibromatosis type 2 (NF2) is an autosomal dominant disease due to chromosome 22 (22q12.2) mutation with a prevalence of 1:33,000-40,000. As many as 50% of cases are familial, 30-60% are genetic mosaic, de novo mutations. Tumor growth in NF often becomes more rapid in pregnancy. Pregnancy with NF2 has a risk of complications of hypertension, preeclampsia, cardiovascular problems, and IUGR (Intrauterine growth restriction). […] A retrospective study in Japan showed that patients with NF2 had survival rates of 5 years, 10 years, and 20 years from diagnosis of 85%, 67%, and 38%, respectively. Pregnant women with neurofibromatosis have an increased risk of morbidity due to the progressive growth of meningiomas and schwannomas, hypertensive/cardiovascular complications, but not death during pregnancy. Additionally, pregnant women with NF2 have a high risk of developing hypertension, preeclampsia, cardiovascular problems, and Intrauterine growth restriction (IUGR).

• #40 Case Report: Rare Case of NF2 in Pregnancy with… | F1000Research

  https://f1000research.com/articles/11-342

  The clinical evaluation and course of the disease was considered stagnant and without any rapid progression, besides a clinical decline in her neurologic and vision from 20 weeks of gestation. Based on the results of periodic evaluations, the progression of neurological deficits was stable. […] Neurofibromatosis can be diagnosed based on the evaluation of clinical symptoms, pedigree analysis, and radiological assessment. Pregnant women with NF2 can experience clinical deterioration due to rapid tumor growth during pregnancy. Patients with neurofibromatosis are advised to undergo genetic, prenatal, and antenatal counseling to better plan pregnancy and prevent lower the risk of inherited disease. NF tumor genetic and molecular testing should be performed to confirm the diagnosis. Multidisciplinary management in tertiary hospitals should be carried out in pregnant women with neurofibromatosis to fetal and maternal morbidity and mortality.

• #41 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-022-13580-9

  We analyzed the clinical and genetic predictors of the functional disability of NF2 patients. Two types of mutations were found to act as predictors, namely Truncating and Mosaic, in addition to Age of symptom onset25. Consequently, we showed that patients of Mild had different functional prognoses compared with other NF2 patients. […] By applying a combination of an NF2 mutation type/location, and age of symptom onset, we classified different degrees of functional preservation and progression, schwannoma growth rate and total interventions per year per patient. The prediction of detailed functional outcomes can be used to plan better strategies for life-long disease management and social integration.

• #42

  https://link.springer.com/article/10.1007/s00401-019-02029-5

  Neurofibromatosis type II (NF2) has a highly variable clinical course, with some patients exhibiting a severe phenotype and development of multiple tumors at an early age, while others may be nearly asymptomatic throughout their lifetime. […] Pathogenic NF2 alterations have a nearly 100% penetrance. Approximately 50% of NF2 patients present with symptoms and/or neoplastic manifestations by the age of 20, and nearly all by the age of 60. […] Patients with truncating alterations that inactivate NF2 exhibit more severe disease, whereas patients with missense loss-of-function mutations typically have a milder disease course. […] Presentation with non-vestibular tumors in early life may be a harbinger of more severe multi-tumor disease. […] Approximately 50% of NF2 cases are suspected to result from hereditary transmission from a parent with NF2, while the remainder appear to be due to de novo mutations in patients with no known family history.

• #43 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9184572/

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #44 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-022-13580-9

  Regardless of treatment, the clinical progression of neurofibromatosis type 2 (NF2), particularly in terms of hearing, swallowing, and gait, tend to worsen throughout the patients lives. […] The functional preservation period and outcome differed significantly depending on clinical/genetic factors. Among these factors, Truncating, Mosaic, and Age of symptom onset25 had the most significant effects on functional disability. […] The prediction of detailed functional outcomes in NF2 patients can plan better strategies for life-long disease management and social integration. […] Several retrospective studies on NF2 have reported genotypephenotype correlations as predictors of disease progression and mortality. […] The resulting clinical predictors have included age of symptom onset and the presence of intracranial meningioma; whereas, the genetic predictions of mortality included truncating and splicing mutations at the 5′-end of the NF2 gene.

• #45 Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype–phenotype correlation with targeted deep sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-022-13580-9

  We analyzed the clinical and genetic predictors of the functional disability of NF2 patients. Two types of mutations were found to act as predictors, namely Truncating and Mosaic, in addition to Age of symptom onset25. Consequently, we showed that patients of Mild had different functional prognoses compared with other NF2 patients. […] By applying a combination of an NF2 mutation type/location, and age of symptom onset, we classified different degrees of functional preservation and progression, schwannoma growth rate and total interventions per year per patient. The prediction of detailed functional outcomes can be used to plan better strategies for life-long disease management and social integration.

• #46 Neurofibromatosis type II – Wikipedia

  https://en.wikipedia.org/wiki/Neurofibromatosis_type_II

  NF2 is a life limiting condition. It is a rare genetic disorder that involves noncancerous tumors of the nerves that transmit balance and sound impulses from the inner ear to the brain. The prognosis is affected by early age onset, a higher number of meningiomas and schwannomas and having a decrease in mutation. […] An early diagnosis is the best way to ensure improvement in management. Although, even with an early diagnosis, some patients still die very young. […] Meningiomas and schwannomas occur in around half of patients with NF2. Meningiomas are tumors that are both intracranial and intraspinal. Schwannomas are tumors that are often centered on the internal auditory canal. Patients with NF2 who have meningiomas have a higher risk of mortality, and the treatment can be very challenging. Individuals who develop schwannomas frequently develop hearing loss and deafness.

• #47 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  NF2-related tumors can affect your life expectancy, depending on their size, location and age at initial diagnosis. […] Your outlook improves if you receive an early diagnosis and treatment before complications happen. […] Your healthcare provider will examine how your symptoms affect you to give you a more accurate prognosis.

• #48 NF2-Related Schwannomatosis (Neurofibromatosis Type 2)

  https://my.clevelandclinic.org/health/diseases/16196-neurofibromatosis-type-2-nf2

  NF2-related tumors can affect your life expectancy, depending on their size, location and age at initial diagnosis. […] Your outlook improves if you receive an early diagnosis and treatment before complications happen. […] Your healthcare provider will examine how your symptoms affect you to give you a more accurate prognosis.

• #49 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Neurofibromatosis type 2 (NF2) is a genetic condition marked by the development of multiple benign tumors in the nervous system. […] The survival period after diagnosis is about 15 years, and the average age at death is between 36 and 39 years, with a 10-year survival rate of 67%. […] Despite benign behavior, NF2-associated tumors result in considerable morbidity and mortality rates. […] Currently, there is no established approach to prevent or cure NF2. […] The advent of molecular biology to scheme the pathogenesis of NF2 can guide to address of new therapeutic potentials for the effective prevention and treatment of NF2-related tumors. […] Genotype-phenotype correlation and the role of NF2 genetic investigation in differentiating NF-related disorders highlight the importance of conducting genetic testing to detect at-risk patients, prognostication, and treatment.

• #50 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The type and severity of NF2 manifestations depend on the type of gene mutation. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The UK NF2 Genetic Severity Score was developed to categorize the patients based on severity into severe, moderate, and mild. […] Generally, NF2 due to truncating mutations (nonsense or frameshift) is more severe and appears at younger ages. […] Patients with truncating mutations are more likely to develop symptoms earlier, have a greater risk of developing at least two CNS tumors in addition to VS, and have a shorter average life expectancy. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] The management of patients with NF2 is typically determined in a multidisciplinary setting.

• #51 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  The type and severity of NF2 manifestations depend on the type of gene mutation. […] Evidence favors a substantial link between genotype and phenotype for NF2-related disorders. […] The UK NF2 Genetic Severity Score was developed to categorize the patients based on severity into severe, moderate, and mild. […] Generally, NF2 due to truncating mutations (nonsense or frameshift) is more severe and appears at younger ages. […] Patients with truncating mutations are more likely to develop symptoms earlier, have a greater risk of developing at least two CNS tumors in addition to VS, and have a shorter average life expectancy. […] The multifocal nature of NF2-related tumors, their proximity to the vital structures, or neural involvement can limit surgical interventions. […] The management of patients with NF2 is typically determined in a multidisciplinary setting.

• #52 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Bevacizumab has shown promise in the treatment of progressive VS in NF2 patients. […] The significant impacts of NF2 on the patients’ quality of life and the severity of symptoms urge the need to explore effective therapies. […] The treatment of NF2 must start with one critical question: how much do the treatment benefits outweigh its risks? […] The available systemic therapies are limited to a handful of choices with limited efficacy. […] A comprehensive understanding of molecular mechanisms in tumor progression of NF2-related tumors will provide opportunities for exploring more efficient treatments.

• #53 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Bevacizumab has shown promise in the treatment of progressive VS in NF2 patients. […] The significant impacts of NF2 on the patients’ quality of life and the severity of symptoms urge the need to explore effective therapies. […] The treatment of NF2 must start with one critical question: how much do the treatment benefits outweigh its risks? […] The available systemic therapies are limited to a handful of choices with limited efficacy. […] A comprehensive understanding of molecular mechanisms in tumor progression of NF2-related tumors will provide opportunities for exploring more efficient treatments.

• #54 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Bevacizumab has shown promise in the treatment of progressive VS in NF2 patients. […] The significant impacts of NF2 on the patients’ quality of life and the severity of symptoms urge the need to explore effective therapies. […] The treatment of NF2 must start with one critical question: how much do the treatment benefits outweigh its risks? […] The available systemic therapies are limited to a handful of choices with limited efficacy. […] A comprehensive understanding of molecular mechanisms in tumor progression of NF2-related tumors will provide opportunities for exploring more efficient treatments.

• #55 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Bevacizumab has shown promise in the treatment of progressive VS in NF2 patients. […] The significant impacts of NF2 on the patients’ quality of life and the severity of symptoms urge the need to explore effective therapies. […] The treatment of NF2 must start with one critical question: how much do the treatment benefits outweigh its risks? […] The available systemic therapies are limited to a handful of choices with limited efficacy. […] A comprehensive understanding of molecular mechanisms in tumor progression of NF2-related tumors will provide opportunities for exploring more efficient treatments.

• #56 The genetic landscape and possible therapeutics of neurofibromatosis type 2 | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-02940-8

  Neurofibromatosis type 2 (NF2) is a genetic condition marked by the development of multiple benign tumors in the nervous system. […] The survival period after diagnosis is about 15 years, and the average age at death is between 36 and 39 years, with a 10-year survival rate of 67%. […] Despite benign behavior, NF2-associated tumors result in considerable morbidity and mortality rates. […] Currently, there is no established approach to prevent or cure NF2. […] The advent of molecular biology to scheme the pathogenesis of NF2 can guide to address of new therapeutic potentials for the effective prevention and treatment of NF2-related tumors. […] Genotype-phenotype correlation and the role of NF2 genetic investigation in differentiating NF-related disorders highlight the importance of conducting genetic testing to detect at-risk patients, prognostication, and treatment.

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