Natural history of neurofibromatosis type 2 with onset before the age of 1 year

• Published in: Neurogenetics Vol. 14; no. 2; pp. 89 - 98
• Main Authors: Ruggieri, Martino, Gabriele, Anna Lia, Polizzi, Agata, Salpietro, Vincenzo, Nicita, Francesco, Pavone, Piero, Platania, Nunzio, Milone, Pietro, Distefano, Angela, Privitera, Giuseppe, Belfiore, Giuseppe, Granata, Francesca, Caltabiano, Rosario, Albanese, Vincenzo, Pavone, Lorenzo, Quattrone, Aldo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-05-2013; Springer Nature B.V
• Subjects: Adolescent; Age of Onset; Biomedical and Life Sciences; Biomedicine; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Child; Children & youth; Disease Progression; Female; Genes, Neurofibromatosis 2 - physiology; Human Genetics; Humans; Infant; Magnetic Resonance Imaging - methods; Male; Molecular Medicine; Mutation - genetics; Neurofibromatosis 2 - diagnosis; Neurofibromatosis 2 - genetics; Neurofibromatosis 2 - pathology; Neurosciences; NMR; Nuclear magnetic resonance; Original Article; Prospective Studies; Retina; Systematic review; Vestibular schwannomas; NF2; Early onset; Neurofibromatosis; Childhood
• ISSN: 1364-6745; 1364-6753
• DOI: 10.1007/s10048-013-0354-0

Neurofibromatosis type 2 (NF2) with onset before the first year of life has been anecdotally reported in the literature. We (a) prospectively (years 1997–2012) followed up three unrelated NF2 children, all harbouring NF2 gene mutations whose onset of disease was before age 1 year, and (b) systematically reviewed published reports on NF2 in the youngest age group (i.e. onset <1 year). The present three children had (1) small (<1 cm), bilateral vestibular schwannomas (VSs) detected (as an incidental finding) at magnetic resonance imaging (MRI) by the age of 4 to 5 months that were asymptomatic for 10 to 14 years, with sudden and rapid (<12 months) progression in two cases at the age of 11 and 15 years, respectively; (2) development of large numbers of skin NF2 plaques mainly in atypical locations (i.e. face, hands, legs and knees), which reverted to normal skin appearance at the time of VSs progression; (3) lens opacities (
n
 = 1) and NF2 retinal changes (
n
 = 2) detected as early as age of 3-4 months; (4) diffuse (asymptomatic) high signal lesions at brain MRI in the periventricular regions (alike cortical dysplasia); and (5) unaffected first-degree relatives who did not harbour
NF2
gene abnormalities. This represents the youngest NF2 group with the longest prospective follow-up so far reported. NF2 may present as a
congenital
form with bilateral VSs presenting as early as the first months of life and with natural history different to that which occurs in classical NF2.