Psychosocial, cognitive, and motor functioning in patients with suspected Sotos syndrome: a comparison between patients with and without NSD1 gene alterations

Abstract

The aim of this study was to investigate psychosocial, cognitive, and motor functioning in patients clinically suspected of Sotos syndrome and to examine differences between patients with deletions or mutations of the gene encoding nuclear SET domain-containing protein 1 (NSD1; the major cause of the syndrome) and those without such alterations. Twenty-nine participants (21 males, 8 females) clinically suspected of Sotos syndrome (mean age 11y 10mo [SD 10y 11mo], range 1y 10mo-48y 5mo) were divided into an NSD1 mutation group (n=12; 8 males, 4 females) and an NSD1 non-mutation group (n=17; 13 males, 4 females). Intelligence, behaviour problems, attention-deficit-hyperactivity disorder (ADHD) symptoms, temperament, adaptive behaviour, and motor functioning were assessed with an extensive test battery. Scores were compared with those of control groups, and scores of the two subgroups were compared with each other. The mean IQ in the 21 individuals tested was 76 (SD 16; range 47-105). High rates of behaviour problems were found and patients lagged 1y 7mo to 2y 7mo behind in aspects of adaptive behaviour. In comparison with a control group of patients with a learning disability, motor functioning was better. NSD1 mutation compared with NSD1 non-mutation patients showed easier temperament, and fewer NSD1 mutation patients scored in the clinical range for 'total behaviour problems' (3/11 vs 13/17), 'internalizing behaviour' (2/11 vs 11/17), and ADHD (0/9 vs 4/15).

Adults with Sotos syndrome: Review of 21 adults with molecularly confirmed NSD1 alterations, including a detailed case report of the oldest person

“…Similar genotype-phenotype correlations are seen in the psychological profiles of affected children: Those with NSD1 point mutations show fewer behavior problems, an easier temperament, and fewer internalizing behaviors [de Boer et al, 2006]. Our review did not have access to details regarding educational or vocational status.…”

Seizures and epilepsy in Sotos syndrome: Analysis of 19 Caucasian patients with long‐term follow‐up

“…Febrile seizures, infantile spasms, absence, tonic-clonic, and myoclonic seizures have been all associated with SS (Tatton-Brown & Rahman, 2007). Furthermore, a wide spectrum of behavioral and emotional disturbances may occur in SS patients, such as attention-deficit-hyperactivity disorder, aggressiveness, irritability, pyromania, social inhibition, psychosis, and autistic features (Mauceri et al, 2000;Tatton-Brown et al, 2005;de Boer et al, 2006). The patients with SS reported herein had FS and/or epilepsy.…”

The behavioral characteristics of Sotos syndrome

“…Improvement has been observed during adolescence [Mauceri et al, ]. Interest in describing the behavioral phenotype of Sotos syndrome has increased recently, particularly with regard to those with and without confirmed NSD1 mutations and deletions [de Boer et al, ].…”

“…The investigation of atypical social behavior has used a variety of methods such as observation [e.g., Mouridsen and Hansen, ], parental reports [e.g., Rutter and Cole, ; Mauceri et al, ] and standardized measures [e.g., Finegan et al, ; Sarimski, ; de Boer et al, ]. Two cohort studies [Finegan et al, ; de Boer et al, ] reported individuals with Sotos syndrome to score higher on the “social scale” of the Child Behavior Checklist [CBCL, Achenbach, ,] compared to the CBCL's normative sample and a range of observational studies have described social difficulties including social withdrawal [e.g., Varley and Crnic, ; Mouridsen and Hansen, ] and difficulties making close friends [e.g., Rutter and Cole, ; Sarimski, ; Compton et al, ].…”

“…Studies have generally reported higher levels of ADHD and/or hyperactivity in participants with NSD1 mutations (i.e., Sotos syndrome) when compared to non NSD1 mutation overgrowth cases [de Boer et al, ]. Other difficulties reported in participants with NSD1 mutations (vs. NSD1 non‐mutations) include aggressive behavior [e.g., Finegan et al, ; Mauceri et al, ; de Boer et al, ] with 55% of individuals with NSD1 mutations showing more aggression than typically developing controls as measured on the CBCL.…”