Evaluation of the impact of the 2021 revised Neurofibromatosis type 1 diagnostic criteria on time to diagnosis

Abstract

Neurofibromatosis type 1 (NF1) has historically been diagnosed clinically based on the NIH Consensus Conference diagnostic criteria. The molecular and clinical knowledge of NF1 has subsequently improved, and an international group of experts published revised diagnostic criteria in 2021, incorporating new diagnostic criteria such as pathogenic variants in NF1. This study aimed to investigate the impact of these new diagnostic criteria on time to diagnosis (TTD) of NF1. A retrospective chart review of individuals evaluated for a diagnosis of NF1 at the Medical Genetics Clinic at Stanford Children's Health was performed. The TTD was determined by calculating the days between their first visit with a medical geneticist for NF1 and the date they would have received a diagnosis based on the previous NF1 diagnostic criteria and the 2021 updated diagnostic criteria. The revised diagnostic criteria for NF1 decreased TTD. The mean difference in TTD was 113 days shorter for the new criteria (p-value = 1.306x À05). This study highlights that the revised 2021 NF1 diagnostic criteria can decrease the TTD. The addition of a heterozygous pathogenic variant in NF1 as a criterion was the change that decreased TTD.

Neurofibromatosis 1 (von Recklinghausen Disease)

“…Although it was difficult for infant patients without a family history to fulfill the previous criteria, it has been reported that the use of the revised diagnostic criteria for NF1 decreased the time to diagnosis. 15 Therefore, the Japanese version of the diagnostic criteria for NF1 should be updated in the near future by the NF1 research group with support from the Ministry of Health, Labour, and Welfare.…”

Autosomal recessive bestrophinopathy combined with neurofibromatosis type 1 in a patient

“…NF1 is caused by pathogenic variants in NF1 gene on chromosome 17q11.2 and characterized by skin pigmentation anomalies such as café-au-lait spots and freckling, as well as dermal neurofibromas. Additionally, NF1 patients frequently have melanocytic iris hamartomas (Lisch nodules), seizures, neurofibromas, learning disabilities, attention deficits, skeletal abnormalities [ 2 , 3 ]. According to the diagnostic criteria of NF1 established by the National Institutes of Health Consensus Conference in 1988, patients with 6 or more café-au-lait spots measuring at least 5 mm in size before puberty, axillary or inguinal freckles and Lisch nodules on the iris could be definitively diagnosed without the requirement of any additional tests [ 4 ].…”