Neurofibromatoses: I. Clinical recommendations for the diagnosis, treatment and multidisciplinary monitoring of children with neurofibromatosis type 1

Abstract

Neurofibromatosis type 1 (MIM 162200) is one of the commonest autosomal dominant disorders in man. The NF1 gene is a large and complex gene localized on chromosome 17q11.2. Several different techniques of DNA analysis have been applied to look for specific mutations in NF1 gene. Clinical diagnosis is based on NIH NF1 criteria. For neurofibromatosis type 1 in children, the main aspects of interdisciplinary care are timely detecting and controlling of treatable complications. For longitudinal monitoring of the development of age-dependent clinical neurofibromatosis type 1 signs and complications, the recommended diagnostic and follow-up protocol for children with Neurofibromatosis type 1 is having an annual review of the following aspects: genetic counseling – at diagnosis; history and physical and neurological examination: general development (neuromotor/cognitive, speech/language function), dermatological (café au lait spots, freckling, cutaneous/subcutaneous and plexiform neurofibromas), skeletal (pseudarthrosis, scoliosis), ocular symptoms, growth measurement (short stature, macrocrania), pubertal development (delayed/precocious puberty), blood pressure check (renal artery stenosis) – yearly; cardiovascular examination (congenital heart disease) – at diagnosis; ophthalmological examination (visual acuity, funduscopy, visual fields, tonometry, ultrasound of eyes and orbit, search for Lisch nodules) – yearly; brain magnetic resonance imaging – at diagnosis >2 year, more frequently only if symptoms or signs are present; electroencephalogram – at diagnosis, later according to clinical indication; abdominal ultrasound (abdominal neurofibromas) – every 5 years; full spine magnetic resonance – at age 15 years; and molecular DNA-based testing (linkage analysis for familiar neurofibromatosis type 1, a pathogenic mutation in NF1 gene for sporadic cases). Children with neurofibromatosis type 1 should present on regular annual basis to a specialist familiar with neurofibromatosis in collaboration with their pediatrician or family practitioner. Treatment of complications of neurofibromatosis type 1 is symptomatic.