50 The Neuropsychological Profile of S/A/3A-Related Disorder/Witteveen-Kolk Syndrome: A Case Study
Authors: Gioia Anthony R , Thomas Nina H 
Published: December 2023

Objective:

The SIN3A gene mutation is a rare genetic mutation with few reported cases (< 1 in 1,000,000) associated with autosomal dominant Witteveen-Kolk Syndrome, a rare neurodevelopmental syndrome only discussed in the past decade (Witteveen et al., 2016). This syndrome can be characterized by short stature, distinctive facial features, developmental delay, mild intellectual disability, autism spectrum disorder, hypotonia, and seizures (Balasubramanian et al., 2021), however a paucity of information regarding comprehensive neuropsychological functioning in these individuals is present in the literature, and even this recent review study noted that intellectual ability was rarely assessed through formal testing (6 of 28 cases). We present a case, “M”, to help describe a potential pattern of neurocognitive strengths and weaknesses in this population.

Participants and Methods:

The participant, “M”, was diagnosed with a de novo mutation in the SIN3A gene at the age of 11 years with previous diagnoses of global developmental delay, hypotonia, autism spectrum disorder, specific learning disability in mathematics, developmental coordination disorder, and attention deficit hyperactivity disorder. M was seen for a comprehensive neuropsychological evaluation at 11 years of age at an academic medical center, which consisted of comprehensive review of medical and school records, parent and child interview, questionnaires, and performance-based testing.

Results:

M’s verbal and language skills emerged as a particular strength. Her verbal memory, verbal fluency, and verbal comprehension skills were all in the average range or above, as were reading, reading comprehension, and spelling skills. M demonstrated a pattern of notable weaknesses in visuospatial skills, including impaired visuospatial reasoning, visuomotor integration, visual scanning, visual perception, and visual memory. Additionally, M demonstrated a slight weakness in Low Average mathematics skills. M also demonstrated fine motor impairment with impaired speed, coordination, and accuracy. Although immediate auditory attention was noted to be average, performance on a test of sustained attention indicated a moderate persistence of attention concerns. Likewise, M’s mother reported her to be very elevated on symptoms of both attention and hyperactivity/impulsivity. Finally, M’s mother reported elevated concerns related to M’s peer relations and atypical behaviors and below average adaptive skills.

Conclusions:

Due to the rarity of M’s de novo mutation in the SIN3A gene, M’s pattern of weaknesses in visuospatial skills, fine motor skills, attention/executive functioning, and social skills, as well as her strengths in verbal skills can aid in further understanding the pattern of cognitive strengths and weaknesses in children with a mutation in the SIN3A gene. Additionally, given her mild weaknesses in math skills, it is possible that M’s performance on mathematics assessments may be impacted by her visuospatial weakness and thus better conceptualized as a visuospatial issue rather than a learning disability. Overall, this case can aid in identifying specific cognitive risk factors, such as visuospatial skills, in this population and lead to more targeted assessment and intervention, and highlights the importance of more nuanced cognitive evaluation as reporting of a general cognitive ability score alone may obscure underlying patterns of cognitive strength and weakness.