Disease name and synonyms
Definition
Main criteria | Additional criteria |
---|---|
Bilateral vestibular schwannomas (VS) or family history of NF2 plus | Unilateral VS plus any two of: meningioma, glioma, neurofibroma, schwannoma, and posterior subcapsular opacities |
1) Unilateral VS or | or |
2) Any two of: meningioma, glioma, neurofibroma, schwannoma, posterior subcapsular lenticular opacities | Multiple meningioma (two or more) plus unilateral VS or any two of: glioma, neurofibroma, schwannoma, and cataract |
Epidemiology
Clinical description
Characteristic | Study | |||
---|---|---|---|---|
Kanter et al. [11] | Evans et al. [1] | Parry et al. [12] | Mautner et al. [13] | |
Number of cases | 73 | 120 | 63 | 48 |
Number of families | 17 | 75 | 32 | 44 |
Sporadic cases | 0 | 45 | 17 | 44 |
Mean age at onset (years) | 20 (of 59) | 22 | 20 | 17 |
Intracranial meningiomas (%) | 18 | 45 | 49 | 58 |
Spinal tumours (%) | NA | 26 | 67 | 90 |
Skin tumours (%) | 32 (of 73) | 68 (of 100) | 67 | 64 |
Café-au-lait macules (%) | 42 (of 31) | 43 (of 100) | 47 | NA |
Cataract (%) | NA | 38 (of 90) | 81 | 62 |
Intracranial astrocytoma (%) | NA | 4.1 | 1.6 | NA |
Ependymoma (%) | NA | 2.5 | 3.2 | 6 |
Optic sheath meningioma (%)1 | NA | 4.1 | 4.8 | 8 |
Etiopathogenesis
Constitutional mutations
MLPA abnormality | Number of occasions (mosaic) |
---|---|
Exon 1-intron1 (deletes intronic CA repeat) | 18 (3) |
Whole gene (exons 1–17) deletion | 16 (2) |
Exons 5–17 deletion | 3 (2) |
Exons 2–3 deletion | 2 |
Exons 2–10 deletion | 2 |
Exons 13–15 deletion | 1 |
Exons 1–16 deletion | 2 (1) |
Exons 1–10 deletion | 3 (1) |
Exons 1–3 deletion | 1 |
Exons 1–4 deletion | 2 (1) |
Exons 1–2 deletion | 1 (1) |
Exons 15–17 deletion | 1 |
Exons 8–17 deletion | 1 |
Exons 8–15 deletion | 1 |
Exon 3 deletion | 1 |
Exon 7 deletion | 1 |
Exon 5 deletion | 1 |
Exons 12–14 duplication | 1 |
Exons 10–16 duplication | 1 |
Exon 2 deletion | 1 |
Exon 8 deletion | 1 |
Exons 2–4 deletion | 1 |
Type of mutation | Detection in 2nd generation (n = 108) | Detection in sporadic non mosaic patients (% non mosaic) | Mosaic mutations (% of mosaic) | Total |
---|---|---|---|---|
Splice site | 35 (32%) | 43 (22%) | 3 (4%) | 80 (15%) |
MLPA positive | 23 (20%) | 28 (14%) | 11 (15%) | 62 (12%) |
FSD | 18 (17%) | 36 (18%) | 20 (26%) | 74 (13%) |
Nonsense | 16 (15%) | 67 (35%) | 28 (37%) | 111 (22%) |
Missense | 7 (6%) | 5 (3%) | 1 (1%) | 13 (2.5%) |
FSI | 3 (3%) | 11 (7%) | 6 (8%) | 20 (4%) |
IFD | 1 (1%) | 1 | 3 (4%) | 5 (1%) |
Ring 22 | 0 | 0 | 3 (4%) | 3 |
Not found | 7 (7%) | 230 (55%) | 158 | 166/529 (31%) |
Total | 108 | 191/421 (45%) | 72 | 529 |
Somatic mutations
Diagnosis
Diagnostic methods
-
Clinical and family history
-
Examination including cutaneous and ophthalmic (Slit lamp)
-
Craniospinal MRI
-
Molecular analysis
Differential diagnosis
Antenatal diagnosis and genetic counselling
Number | PRE testing Mosaic inferred | PRE testing Transmission risk | POST genetic negative testing in blood Mosaic inferred | POST genetic negative testing in blood Transmission risk | |
---|---|---|---|---|---|
< 20 BVS | 85 | 12% | 45% | 46% | 30% 1 in 3 |
< 20 UVS | 21 | 42% | 33% | 87% | 11% 1 in 9 |
20–29 BVS | 67 | 27% | 36% | 78% | 16% 1 in 6 |
20–29 UVS | 27 | 78% | 19% | 97% | 8% 1 in 12 |
30–39 BVS | 54 | 50% | 28% | 88% | 11% 1 in 9 |
30–39 UVS | 19 | 85% | 12% | 98% | 6% 1 in 16 |
40+ BVS | 53 | 63% | 22% | 93% | 9% 1 in 11 |
40+ UVS | 34 | 90% | 10% | 99% | 5% 1 in 20 |