Andre Rietman

Neurofibromatosis type 1 (NF1) is a genetic disorder or syndrome caused by changes in the NF1 gene on chromosome 17q11.2. NF1 occurs in 1:2,000 to 4,000 people, of whom about half are ‘new mutations’ meaning parents do not have NF1. NF1 leads to symptoms in the appearance of people, such as light brown spots on the skin (so-called café-au-lait macules), lumps on or in the skin but also to an increased risk of having benign and malignant tumors. There is a 7-13% lifetime risk of developing malignant peripheral nervesheath tumors. Most symptoms occur in the nervous system, the skin, and the bones. This leads to unpredictable and variable complications. In adults, sex and age do not seem to be associated with NF1 severity, but there appears to be an association with general quality of life. Although the diagnostic criteria are largely somatic and the physical symptoms are serious and impressive, cognitive deficits and behavioral problems are the most common complications of NF1 in children.

Genotype is the genetic makeup or code of cells or of an organism. The genotype, together with other genetic and environmental factors determines one's phenotype. The phenotype of an organism is the combination of characteristics, including the physical appearance and properties, development, and behavior. A behavioral phenotype includes cognitive, personality, and behavioral patterns. Some behavioral phenotypes may be psychiatric disorders or syndromes. Neurocognitive and psychosocial assessments can provide a profile of strengths and weaknesses, a behavioral phenotype of the cognitive, sensory, motor, educational, behavioral, social, and emotional characteristics of people with NF1.

Behavioral phenotype of NF1

The average full-scale intelligence quotient (IQ) of children with NF1 is about 10 to 15 points lower than the IQ in the general population and also compared to siblings without NF1. Intellectual disability is twice as common in NF1 and there are more individuals with NF1 who have an IQ below 70. Other cognitive problems in NF1 are associated with speech and language, visuospatial skills, executive functions (inhibition, planning, and flexibility), attention, and motor performance. The majority of the behavioral problems found in NF1 are emotional problems such as anxiety, depression, and social withdrawal. The most common behavioral disorder in NF1 is ADHD (attention-deficit/hyperactivity disorder): ADHD occurs in 30 to 50% of the children with NF1 (compared to 5% of children in the general population). They also have poorer social skills and there is an increased risk of autism spectrum disorders (ASD).