Jenny Garzon1, Andrea Patete2, Carolyn Serbinski1, Madison Hankins1, Michael Sawin1, Allison Weisman3, Katherine Kim3, Joel Charrow3, Robert Listernick3, Carlos Prada3
1Department of Genetics, Ann & Robert H. Lurie Children's Hospital of Chicago, 2Lincoln Memorial University, 3Department of Genetics, Ann & Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Feinberg School of Medicine, Northwestern University
Objective:
To describe the neurocognitive manifestations in patients with NF1 microdeletion syndromes.
Background:
Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome that affects 1 in 2500-3000 people. About 5-11% of NF1 patients have NF1 microdeletion syndrome, historically associated with a higher risk of intellectual disability than the NF1 population.
Design/Methods:
We performed a retrospective study of pediatric patients with molecularly confirmed NF1 microdeletion syndrome seen in the Neurofibromatosis Clinic of the Ann & Robert H. Lurie Children’s Hospital of Chicago from 01/01/2000 to 09/01/2022. Clinical data was collected from medical records.
Results:
A total of 12 patients were identified with NF1 microdeletions. The mean age at diagnosis was 2.38 years (range 3 months to 5 years), and 58% were female. The most common deletion was type 1 (1.4-MB). Macrocephaly was present in 33% of individuals. One individual presented with a symptomatic chiasmatic optic pathway glioma. Plexiform neurofibromas were reported in 4 (33%) without any known malignant transformation. Neurodevelopmental manifestations included speech difficulties (expressive/receptive) in 8 (66%), attention-deficit/hyperactivity disorder (ADHD) in 5 (42%), gross motor delays in 4 (33%), fine motor delays in 4 (33%), and autism spectrum disorders in 3 (25%). There were 2 adults with NF1 microdeletions attending college. Other comorbidities include anxiety (6, 50%), depression (3, 25%), and sleep disturbances (5, 42%).
Conclusions:
In this Study, NF1microdeletion patients were diagnosed at an early age. NF1 microdeletion individuals have variable neurological and neurodevelopmental manifestations which require tailored developmental interventions. Sleep difficulties appear common in this cohort in addition to other neurological manifestations. Two adults with NF1 microdeletions were in College suggesting that, at least in some individuals, the neurocognitive outcome may be better than has previously been described.