Neurocutaenous syndromes Year 4 Paediatrics Notes OmpathStudy

Neurocutaenous syndromes Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / NEONATOLOGY -- Slide 1 Neurocutaenous Syndromes Dr Rose Munge Slide 2 The neurocutaneous syndromes include a heterogeneous group of disorders characterized by abnormalities of both the integument and central nervous system (CNS) of variable severity.\nMany of the disorders are hereditary and believed to arise from a defect in differentiation of the primitive ectoderm (nervous system, eyeball, retina, and skin).\nDisorders classified as neurocutaneous syndromes include neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), tuberous sclerosis complex (TSC), Sturge- Weber syndrome (SWS), von Hippel–Lindau disease (VHL), PHACE (posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, cardiac defects, eye abnormalities) syndrome, ataxia-telangiectasia (AT), linear nevus syndrome, hypomelanosis of Ito, and incontinentia pigmenti. Slide 3 Neurofibromatosis The neurofibromatoses are autosomal dominant disorders that cause tumors to grow on nerves and result in other systemic abnormalities.\n There are three types, neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis, all of which are clinically and genetically distinct diseases and should be considered separate entities. Slide 4 Clinical Manifestations and Diagnosis NF1 has an incidence of 1 in 3,000 live births and is caused by autosomal dominant loss-of-function mutations in the NF1 gene.\n50% are inherited from an affected parent, and the other 50% result from a sporadic gene mutation. The disease is clinically diagnosed when any two of the following seven features are present:\n(1) six or more café-au-lait macules 5 mm in greatest diameter in prepubertal individuals and 15 mm in greatest diameter in post pubertal individuals.\nCafé-au-lait macules (CALMs) are the hallmark of neurofibromatosis and are present in almost 100% of patients. They are present at birth but increase in size, number, and pigmentation, especially during the first few years of life.\nThe CALMs are scattered over the body surface, with predilection for the trunk and extremities. Slide 5 (2) Axillary or inguinal freckling consisting of multiple hyperpigmented areas 2-3 mm in diameter.\nSkinfold freckling usually appears between 3 and 5 yr of age.\nThe frequency of axillary and inguinal freckling is reported to be 80% by 6 yr of age.\n(3) Two or more iris Lisch nodules, which are hamartomas located within the iris and are best identified by a slit-lamp examination. They are present in more than 74% of patients with NF1.\nThe prevalence of Lisch nodules increases with age, from only 5% of children younger than 3 yr of age, to 42% among children 3-4 yr of age, and virtually 100% of adults older than 21 yr of age. Slide 6 (4) Two or more neurofibromas or one plexiform neurofibroma.\nNeurofibromas are most visible on the skin, but they may occur on any peripheral nerve in the body, including along peripheral nerves and blood vessels and within viscera, including the gastrointestinal tract.\nThey are usually small, rubbery lesions with a slight purplish discoloration of the overlying skin.\nPlexiform neurofibromas are typically congenital and result from diffuse thickening of nerve trunks and surrounding soft tissues.\nThe skin overlying a plexiform neurofibroma may be coarse and associated with hyperpigmentation.\nPlexiform neurofibromas may produce overgrowth of an extremity and a deformity of the corresponding bone. Slide 7 (5) A distinctive osseous lesion such as sphenoid dysplasia (which may cause pulsating exophthalmos) or cortical thinning of long bones with or without pseudoarthrosis (most often the tibia).\n(6) Optic gliomas are present in approximately 15–20% of individuals with NF1; ~ 30% of these are clinically symptomatic and require tumor-directed therapy.\nThey are the most frequently observed CNS tumor in NF1.\nBecause of visual acuity compromise, it is recommended that all children with NF1 undergo at least annual ophthalmologic examinations, or more frequent ones if there is a concern.\nThe most common time to develop symptoms is between the ages of 2-6 yr; they manifest as a change in visual acuity, a change in the visual fields, or pallor of the optic nerve. Extension into the hypothalamus can lead to precocious puberty. (7) A first-degree relative with NF1 whose diagnosis was based on the aforementioned criteria. Slide 10 Children with NF1 are susceptible to neurologic complications such as learning disabilities, attention-deficit disorders, behavioral and psychosocial problems, and abnormalities of speech among affected children.\nLearning disability affects more than half of individuals with NF1.\nSeizures are observed in approximately 8% of NF1 patients.\nThe cerebral vessels may develop aneurysms or stenosis consistent with moyamoya syndrome. Neurologic sequelae of these vascular abnormalities include tran