Behavioral phenotype and sleep problems in SATB2‐associated syndrome

Abstract

Aim To determine the nature and frequency of behavioral phenotypes and sleep disturbances in individuals with SATB2‐associated syndrome (SAS). Method The Strengths and Difficulties Questionnaire (SDQ) and an age‐appropriate sleep questionnaire were distributed to the parents of individuals with SAS. All scores were compared to available normative data. Results Thirty‐one individuals completed the assessment (18 females, 13 males; mean age 7y 4mo [SD 4y 1mo], range 2–16y). Individuals with SAS had significantly higher Total Difficulty scores than the normative sample (14.9 [SD 5.8] vs 7.1 [SD 5.7], p<0.001). A high frequency of emotional problems (22.6% vs 8%, p=0.01), peer problems (48.4% vs 10%, p<0.001), hyperactivity (48.4% vs 9%, p<0.001), and low prosocial behaviors (45.2% vs 9%, p<0.001) contribute to the behavioral profile in SAS. Concurrent sleeping difficulties were also frequently identified. Ten individuals in the 5 to 15 years age range had at least one sleep disorder (mean Sleep Disturbance Scale for Children total score 40.9 [SD 8.4] vs 35.1 [SD 7.7], p<0.001). Interpretation With previous limited available objective neurobehavioral data on the SAS population, we reported evidence of high‐risk for a broad spectrum of burdensome behavioral phenotype and concurrent sleeping difficulties, the latter being particularly prevalent during early childhood. Routine assessment and treatment for behavioral issues and sleep problems is recommended. What this paper adds Emotional and peer problems, hyperactivity, and low prosocial behavior are common in SATB2‐associated syndrome. The Strength and Difficulties Questionnaire Total Difficulty scores are atypical in nearly half of individuals. Behavioral difficulties are perceived as burdensome to over half of the parents. Nearly half of individuals have at least one sleep disorder. Sleep–wake transition disorders were most common.

SATB2-associated syndrome caused by a novel SATB2 mutation in a Chinese boy: A case report and literature review

“…A broad spectrum of behavioral issues has been reported, including pleasant personality, irritability, hyperactivity, sleep problems, sensory issues, stereotyped repetitive movements, and Rett syndrome-like phenotypes[ 3 , 7 , 22 , 27 , 28 ]. Nonspecific brain abnormalities detected by MRI are found in half of affected individuals, including ventricle enlargements, thin corpus callosum, enlarged perivascular spaces, and abnormal myelinization in white matter[ 7 , 22 ].…”

Abnormalities in pharyngeal arch‐derived structures in SATB2‐associated syndrome

“…SATB2-associated syndrome (SAS; glass syndrome, OMIM 612313) is a multisystemic autosomal dominant disorder with a well-established neurodevelopmental phenotype characterized by severe speech delay, autistic tendencies, and behavioral abnormalities. [1][2][3] From the craniofacial perspective, individuals with SAS are known to have a high frequency of palatal and dental anomalies often related to morphological changes affecting the jaw and lower face including micrognathia, facial asymmetry, a triangular appearance of the lower face, and a prominent chin. 4,5 Since Satb2 was identified as a gene associated with cleft palate in humans, 6 experiments in mice and other vertebrates have shown that Satb2 is expressed early in development in the first pharyngeal arch (PA1), the tissue that later gives rise to the jaw.…”

“…SATB2‐associated syndrome (SAS; glass syndrome, OMIM 612313) is a multisystemic autosomal dominant disorder with a well‐established neurodevelopmental phenotype characterized by severe speech delay, autistic tendencies, and behavioral abnormalities 1–3 . From the craniofacial perspective, individuals with SAS are known to have a high frequency of palatal and dental anomalies often related to morphological changes affecting the jaw and lower face including micrognathia, facial asymmetry, a triangular appearance of the lower face, and a prominent chin 4,5 …”

Quantitative Phenotype Morbidity Description of SATB2-Associated Syndrome

“…Likewise, composite nonverbal cognitive scores can display variability from mild to severe [3,7]. The broad range in severity can also be found for many of the other systemic features, including seizures (some individuals have severe epileptic encephalopathy), behavioral problems (antipsychotic medications or management at inpatient facilities for mental health issues have been reported), sleeping difficulties (including the need for high doses of multiple medications to aid with sleep), skeletal complications (some individuals have had recurrent fractures requiring treatment with medications for metabolic bone issues), dental anomalies (significant primary and secondary dentition problems have been reported), and growth delay (some individuals have needed aggressive feeding interventions) [8][9][10][11][12][13][14][15][16][17].…”