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Human Genetics Feb 2022Neurofibromatosis type 1 (NF1) is the most frequent disorder associated with multiple café-au-lait macules (CALM) which may either be present at birth or appear during... (Review)
Review
Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants.
Neurofibromatosis type 1 (NF1) is the most frequent disorder associated with multiple café-au-lait macules (CALM) which may either be present at birth or appear during the first year of life. Other NF1-associated features such as skin-fold freckling and Lisch nodules occur later during childhood whereas dermal neurofibromas are rare in young children and usually only arise during early adulthood. The NIH clinical diagnostic criteria for NF1, established in 1988, include the most common NF1-associated features. Since many of these features are age-dependent, arriving at a definitive diagnosis of NF1 by employing these criteria may not be possible in infancy if CALM are the only clinical feature evident. Indeed, approximately 46% of patients who are diagnosed with NF1 later in life do not meet the NIH diagnostic criteria by the age of 1 year. Further, the 1988 diagnostic criteria for NF1 are not specific enough to distinguish NF1 from other related disorders such as Legius syndrome. In this review, we outline the challenges faced in diagnosing NF1 in young children, and evaluate the utility of the recently revised (2021) diagnostic criteria for NF1, which include the presence of pathogenic variants in the NF1 gene and choroidal anomalies, for achieving an early and accurate diagnosis.
Topics: Brain Neoplasms; Cafe-au-Lait Spots; Child; Child, Preschool; Colorectal Neoplasms; Diagnosis, Differential; Female; Genes, Neurofibromatosis 1; Genetic Variation; Humans; Infant; Infant, Newborn; Male; Mosaicism; Neoplastic Syndromes, Hereditary; Neurofibromatosis 1
PubMed: 34928431
DOI: 10.1007/s00439-021-02410-z -
Journal of Ophthalmology 2016Neurofibromatosis type 1, tuberous sclerosis complex, and Von Hippel-Lindau disease, historically classified as the phakomatoses, are hereditary multisystem disorders... (Review)
Review
Neurofibromatosis type 1, tuberous sclerosis complex, and Von Hippel-Lindau disease, historically classified as the phakomatoses, are hereditary multisystem disorders characterized by the presence of hamartoma, which carry the risk of malignant transformation. The alteration of tumor suppressor genes seems to be at the basis of their pathophysiogenetic mechanism. Lisch and choroidal nodules in neurofibromatosis type 1, retinal astrocytomas in tuberous sclerosis complex, and retinal capillary hemangioma in Von Hippel-Lindau disease are the principal ophthalmic hamartomatous manifestations. The advent of novel imaging techniques such as near infrared reflectance and optical coherence tomography has provided unprecedented insight on the choroidal and retinal features of these diseases. These methods have improved early diagnosis and the ongoing surveillance in these conditions. Among an array of treatment modalities, antivascular endothelial growth factor therapy has been used in the management of retinal hamartomas but results have been varied. This review is an update on the pathophysiogenetic mechanisms, ophthalmic manifestations, and novel treatment strategies in the phakomatoses with emphasis on the role of imaging techniques.
PubMed: 27493794
DOI: 10.1155/2016/3043026 -
Dermatology Online Journal Dec 2005A 74-year-old man presented with skin-colored nodules in his left antecubital fossa. The lesions had been present for 35 years and were asymptomatic. Nodules elsewhere...
A 74-year-old man presented with skin-colored nodules in his left antecubital fossa. The lesions had been present for 35 years and were asymptomatic. Nodules elsewhere on the body, cafe-au-lait spots, axillary freckling, and Lisch nodules were absent. No family members had similar nodules. A diagnosis of segmental neurofibromatosis was made, and a biopsy specimen of a nodule showed a neurofibroma. As the patient had no complications of neurofibromatosis 1, no treatment was needed.
Topics: Aged; Humans; Male; Neurofibromatoses; Skin; Skin Neoplasms
PubMed: 16403392
DOI: No ID Found -
Medical Journal, Armed Forces India 2023Neurofibromatosis (NF) is an inherited neuroectodermal abnormality that primarily affects the growth of neural tissues, and Riccardi classified it into eight types....
Neurofibromatosis (NF) is an inherited neuroectodermal abnormality that primarily affects the growth of neural tissues, and Riccardi classified it into eight types. Segmental neurofibromatosis, which is a rare form of neurofibromatosis, is classified as type 5. We report a case for very unusual presentation of segmental NF with unilateral lisch nodules and uncommon sites involving the scalp. Moreover, we could find only one case report of segmental NF with lisch nodules in the literature and could not find any case report involving the scalp.
PubMed: 37193521
DOI: 10.1016/j.mjafi.2020.11.021 -
Translational Vision Science &... Feb 2022To determine the prevalence of choroidal abnormalities (CAs) and Lisch nodules (LNs) in children who met the clinical diagnostic criteria (CDC) alone and those with a... (Observational Study)
Observational Study
PURPOSE
To determine the prevalence of choroidal abnormalities (CAs) and Lisch nodules (LNs) in children who met the clinical diagnostic criteria (CDC) alone and those with a molecularly confirmed diagnosis (MCD) of neurofibromatosis type 1 (NF1), and to ascertain any differences between the groups.
METHODS
This was a cross-sectional observational study. All children who met the CDC and/or had MCD of NF1 and underwent eye examination were included. At least two CAs or LNs between the two eyes were set as a threshold to define the presence of either abnormality. Frequencies alongside 95% confidence intervals (CIs) were calculated. The relationship between patient age and the presence of LNs and/or CAs was estimated using logistic regression.
RESULTS
The study cohort included 94 patients; CAs (64%) were more prevalent than LNs (41%) (0.22; 95% CI, 0.08-0.36; P = 0.0023). The probability of the presence of LNs was lower than that of CAs across all ages (odds ratio = 0.37; 95% CI, 0.20-0.69; P = 0.00173). CAs were exclusively found in 37% of patients and LNs in 16%; 80% had either CAs or LNs, or both. In the CDC group (n = 41), the difference in prevalence (CAs = 68%, LNs = 51%) did not attain statistical significance (0.17; 95% CI, -0.06 to 0.40; P = 0.18). In the MCD group (n = 53), the difference in prevalence (CAs = 60%, LNs = 34%) was significant (0.26; 95% CI, 0.006-0.47; P = 0.023).
CONCLUSIONS
CAs were more frequent than LNs in pediatric NF1 patients regardless of age and MCD status. Combining ophthalmological exams with near-infrared imaging will increase the diagnostic reach in pediatric NF1.
TRANSLATIONAL RELEVANCE
CAs detected on near-infrared imaging are objective biomarkers in NF1. They are more prevalent and detected earlier in the pediatric population compared with LNs. Hence, the presence of CAs should be routinely ascertained in children suspected with NF1.
Topics: Child; Choroid; Cross-Sectional Studies; Hamartoma; Humans; Neurofibromatosis 1; Prevalence
PubMed: 35119474
DOI: 10.1167/tvst.11.2.10 -
International Journal of Molecular... Aug 2023Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of... (Review)
Review
Neurofibromatosis type 1 (NF1) is a rare inherited neurocutaneous disorder with a major impact on the skin, nervous system and eyes. The ocular diagnostic hallmarks of this disease include iris Lisch nodules, ocular and eyelid neurofibromas, eyelid café-au-lait spots and optic pathway gliomas (OPGs). In the last years, new manifestations have been identified in the ocular district in NF1 including choroidal abnormalities (CAs), hyperpigmented spots (HSs) and retinal vascular abnormalities (RVAs). Recent advances in multi-modality imaging in ophthalmology have allowed for the improved characterization of these clinical signs. Accordingly, CAs, easily detectable as bright patchy nodules on near-infrared imaging, have recently been added to the revised diagnostic criteria for NF1 due to their high specificity and sensitivity. Furthermore, subclinical alterations of the visual pathways, regardless of the presence of OPGs, have been recently described in NF1, with a primary role of neurofibromin in the myelination process. In this paper, we reviewed the latest progress in the understanding of choroidal and retinal abnormalities in NF1 patients. The clinical significance of the recently revised diagnostic criteria for NF1 is discussed along with new updates in molecular diagnosis. New insights into NF1-related neuro-ophthalmic manifestations are also provided based on electrophysiological and optical coherence tomography (OCT) studies.
Topics: Humans; Neurofibromatosis 1; Choroid; Neurofibromatoses; Skin; Eyelids
PubMed: 37686284
DOI: 10.3390/ijms241713481 -
Oman Journal of Ophthalmology Sep 2013Iris tumors are broadly classified into cystic or solid lesions. The cystic lesions arise from iris pigment epithelium (IPE) or iris stroma. IPE cysts classically remain... (Review)
Review
Iris tumors are broadly classified into cystic or solid lesions. The cystic lesions arise from iris pigment epithelium (IPE) or iris stroma. IPE cysts classically remain stable without need for intervention. Iris stromal cyst, especially those in newborns, usually requires therapy of aspiration, possibly with alcohol-induced sclerosis, or surgical resection. The solid tumors included melanocytic and nonmelanocytic lesions. The melanocytic iris tumors include freckle, nevus (including melanocytoma), Lisch nodule, and melanoma. Information from a tertiary referral center revealed that transformation of suspicious iris nevus to melanoma occurred in 4% by 10 years and 11% by 20 years. Risk factors for transformation of iris nevus to melanoma can be remembered using the ABCDEF guide as follows: A=age young (<40 years), B=blood (hyphema) in anterior chamber, C=clock hour of mass inferiorly, D=diffuse configuration, E=ectropion, F=feathery margins. The most powerful factors are diffuse growth pattern and hyphema. Tumor seeding into the anterior chamber angle and onto the iris stroma are also important. The nonmelanocytic iris tumors are relatively uncommon and included categories of choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid, leukemic, secondary, and non-neoplastic simulators. Overall, the most common diagnoses in a clinical series include nevus, IPE cyst, and melanoma. In summary, iris tumors comprise a wide spectrum including mostly iris nevus, IPE cyst, and iris melanoma. Risk factors estimating transformation of iris nevus to melanoma can be remembered by the ABCDEF guide.
PubMed: 24379549
DOI: 10.4103/0974-620X.122269 -
The West Indian Medical Journal Dec 2014Neurofibromatosis 1 is the commonest neurocutaneous autosomal dominant disorder with full penetrance, although expression may not be complete by the age of five years....
Neurofibromatosis 1 is the commonest neurocutaneous autosomal dominant disorder with full penetrance, although expression may not be complete by the age of five years. Lisch nodules, however, are predominantly visible in children usually after the age of six years. Therefore, it is important to appreciate that their absence before this age does not pre-empt the diagnosis. A child being treated for hypertension of unknown aetiology with cafe au lait lesions presented to the ophthalmologist with blurred vision. Clinical examination revealed Lisch nodules which confirmed the suspicion of neurofibromatosis 1 as per National Institutes of Health criteria. The aim of this report is to highlight the importance of regular ophthalmic screening, both in suspected and confirmed cases, as these patients have long-term sequelae.
PubMed: 25867571
DOI: 10.7727/wimj.2013.323