Cognitive and behavioral functioning in two neurogenetic disorders; how different are these aspects in Duchenne muscular dystrophy and Neurofibromatosis type 1?

Abstract

The presence of neurocognitive and behavioral problems are common features in various neurogenetic disorders. In Duchenne muscular dystrophy (DMD), these problems have been linked to mutations along the dystrophin gene affecting different brain dystrophin isoforms. However, comparable cognitive and behavioral problems have been found in Neurofibromatosis type 1 (NF1). This study aims to assess disorder specific differences in cognition and behavior between DMD and NF1. Retrospective data of 38 male patients with DMD were aged-matched with data of 38 male patients with NF1. Patients of both groups underwent neurocognitive assessment for regular clinical care. Intellectual abilities, sequential and simultaneous processing, verbal memory and sustained attention were evaluated. In addition, parents and teachers completed behavioral questionnaires. Males with DMD exhibited low intellectual abilities and sequential processing problems, but these outcomes not significantly differed from males with NF1. Simultaneous processing, verbal memory and sustained attention outcomes were equal for both groups. Outcomes of questionnaires displayed higher rates of aggressive behavior (13.2%) in DMD, whereas in NF1 higher rates of problems with thinking (15.8%), withdrawn (10.5%) and social behavior (10.5%) were noticed. In the neurogenetic disorders DMD and NF1, on average overlapping cognitive and behavioral problems are noticed, suggesting that these are not only caused by gene mutations resulting in a lack of one specific protein.

Fig 1. Flowchart of inclusion.

Note: DMD = Duchenne muscular dystrophy, NF1 = Neurofibromatosis type 1.

Fig 2. Frequencies of the Wechsler full-scale intelligence quotient scores of the DMD (N = 38) and NF1 group (n = 38).

FSIQ = full-scale intelligence quotient, DMD = Duchenne muscular dystrophy, NF1 = Neurofibromatosis type 1. FSIQ mean scores are displayed using frequencies of the group DMD (white) and group NF1 (grey) patients.

Fig 3. Mean (SD) outcomes of z-scores of the DMD group (N = 38) and NF1 (N = 38) group.

SEQ = Sequential processing, SIM = Simultaneous processing, SVAS = Sustained Visual Attention Speed, SVAA = Sustained Visual Attention Accuracy, SAU = Sustained Auditory Attention, IR = immediate recall, DR = delayed recall, DMD = Duchenne muscular dystrophy, NF1 = Neurofibromatosis type 1. ** p < .001 (two-sided). The outcomes are frequencies of the mean outcomes. The statistical method used to compare the outcomes of KABC SEQ processing and SIM processing within the DMD or NF1 group was the paired sample t-test. The z-scores represent the mean outcomes and standard deviations on cognitive outcomes of each group.