Neuropsychological Functioning in Individuals with Noonan Syndrome: a Systematic Literature Review with Educational and Treatment Recommendations

Abstract

Noonan syndrome (NS) is a relatively common genetic syndrome with variable features including short stature, congenital heart disease, distinctive facial characteristics, skeletal anomalies, and varying degrees of developmental delay. NS is caused by gene mutations in a cellular signaling pathway that is essential for typical growth and development. Research in the past few decades has revealed that individuals with NS have highly variable neurocognitive and behavioral outcomes. To a certain extent, variability in cognitive functioning depends on the particular gene where a mutation is found; additionally, factors related to medical severity and environmental effects contribute substantially to outcomes. This article contains a systematic review of research on neuropsychological features of NS, including cognition, motor development, language, memory, attention, visual perception, adaptive behavior, social skills, and mental health concerns. Given the wide variety of possible cognitive and behavioral complications associated with NS, it is recommended that clinical neuropsychological evaluation of cognitive, adaptive, and psychological domains of functioning should be standard of care for all individuals with NS. Suggested considerations for assessment of individuals with NS are provided. The paper concludes with recommendations for educational and therapeutic interventions, as well as suggestions for future research directions.

Genetic contribution to neurodevelopmental outcomes in congenital heart disease: are some patients predetermined to have developmental delay?

“…Increasing evidence also suggests that while the majority of children with Noonan syndrome function in the general education setting, reduced executive functioning and high rates of ADHD are often present. [30, 31] Children with cardiofaciocutaneous syndrome may have similar facial, growth, and cardiac features but typically have more severely affected cognitive status. [32] Children with Costello syndrome have cognitive issues that fall on a spectrum between Noonan syndrome and cardiofaciocutaneous syndrome; developmental delay or intellectual disability is present in all individuals.…”

Personality and Psychopathology in Adults with Noonan Syndrome

“…Because only patients were included who could complete the MMPI-2-RF, the sample consisted of relatively more patients with higher IQ scores-hence more patients with a mutation in SOS1. Other studies also found patients with a mutation in SOS1 to have more favourable outcomes regarding intellectual functioning than patients with PTPN11 (Pierpont, 2016). Furthermore, patients with psychological or cognitive problems may be overrepresented in this study, because they could be more inclined to participate or were more likely to bereferred for neuropsychological assessment, which might have consequences for the generalization of the findings of this study to the general NS population.…”

“…Regarding cognitive functioning, NS is associated with varying degrees of developmental delay and intelligence scores tend to vary from intellectual disability to superior levels of functioning. However, most patients with NS show intellectual abilities within the (low)average range (Pierpont, 2016). In children and adolescents with NS, cognitive difficulties in language functioning, visual processing, motor abilities, attention and executive functioning, memory and social functioning have been found (Pierpont, 2016).…”

“…However, most patients with NS show intellectual abilities within the (low)average range (Pierpont, 2016). In children and adolescents with NS, cognitive difficulties in language functioning, visual processing, motor abilities, attention and executive functioning, memory and social functioning have been found (Pierpont, 2016). Studies regarding cognitive functioning in adults are scarce, but mainly report a lowered speed of information processing, subjective executive difficulties and social cognitive problems (e.g.…”

Variability in clinical and neuropsychological features of individuals with MAP2K1 mutations

“…Intellectual disability is reported in approximately 90–100% CFC patients [Kavamura et al, ; Yoon et al, ] but only 6–23% of NS patients [van der Burgt et al, Pierpont et al, ]. While children with NS rarely have severe intellectual impairments, milder neuropsychological concerns are often evident, especially within particular aspects of learning and memory, attention regulation, or social development [Pierpont, ].…”