Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: An update
adolescent; Autism; parent; development; cognition; behavior; Developmental delay; problem behavior; priority journal; case study; interpersonal communication; preschool child; observational study; unclassified drug; childhood; human; article; child; female; male; adult; clinical article; young adult; automutilation; 7 dehydrocholesterol/ec [Endogenous Compound]; 8 dehydrocholesterol/ec [Endogenous Compound]; adaptive behavior; aggression; cerebrospinal fluid level; child rearing; cholesterol/ec [Endogenous Compound]; intelligence quotient; Smith Lemli Opitz syndrome; Smith-Lemli-Opitz syndrome; socialization; Stanford-Binet Intelligence Scale; Sterols; walking; behavior; tone and motor problems; trajectory; characteristics; aggression; development; delayed development
Background: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior. Methods: This was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants. Results: Developmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group. Conclusions: A history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials.
Thurm A; Tierney E; Farmer C; Albert P; Joseph L; Swedo S; Bianconi S; Bukelis I; Wheeler C; Sarphare G; Lanham D; Wassif C A; Porter F D
Journal of Neurodevelopmental Disorders
2016
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1186/s11689-016-9145-x" target="_blank" rel="noreferrer noopener">10.1186/s11689-016-9145-x</a>
Preliminary Study of Neurodevelopmental Outcomes and Parenting Stress in Pediatric Mitochondrial Disease
emotion; child behavior; priority journal; intellectual impairment/dm [Disease Management]; prognosis; preschool child; parental stress; human; article; child; female; male; quality of life; clinical article; daily life activity; disease severity; aggression; intelligence quotient; childhood disease/dm [Disease Management]; comorbidity; Leigh disease/dm [Disease Management]; MELAS syndrome/dm [Disease Management]; nervous system development; problem behavior/dm [Disease Management]; anxiety disorder/dm [Disease Management]; attention disturbance/dm [Disease Management]; brain atrophy/dm [Disease Management]; delinquency; depression/dm [Disease Management]; drug resistant epilepsy/dm [Disease Management]; drug resistant epilepsy/dr [Drug Resistance]; intelligence; lactic acidosis/dm [Disease Management]; muscle disease/dm [Disease Management]; neuroimaging; nuclear magnetic resonance imaging; postnatal depression/dm [Disease Management]; psychomotor development; sleep disorder/dm [Disease Management]; social problem; somatization/dm [Disease Management]; thinking impairment/dm [Disease Management]; behavioral problems; Leigh syndrome; mitochondrial disorders; MELAS syndrome; trajectory; characteristics
Background Little is known regarding the neuropsychological profiles of pediatric patients with mitochondrial diseases or their parents, information that is crucial for improving the quality of life (QOL) for both patients and parents. We aimed to delineate neurodevelopment and psychological comorbidity in children with mitochondrial diseases in the preliminary investigation of adequate intervention methods, better prognoses, and improved QOL for both patients and parents. Methods Seventy children diagnosed with mitochondrial diseases were neuropsychologically evaluated. Neurocognitive (development, intelligence) and psychological (behavior, daily living function, maternal depression, parenting stress) functions were analyzed. Clinical variables, including the first symptom, epileptic classification, organ involvement, lactic acidosis, brain magnetic resonance imaging findings, muscle pathology, biochemical enzyme assay results, and syndromic diagnosis of mitochondrial diseases, were also reviewed. Results Prediagnostic assessments indicated that cognitive and psychomotor developments were significantly delayed. Group mean full scale intelligence quotient (IQ) scores indicated mild levels of intellectual disability, borderline levels of verbal IQ impairment, and mild levels of intellectual disability on performance IQ. Many children exhibited clinically significant levels of behavioral problems, whereas mothers of children with mitochondrial diseases exhibited significant increases in parenting stress relative to mothers of healthy children. Furthermore, 65% of mothers exhibited significant levels of depression. Early onset of the first symptoms, diffuse brain atrophy, and drug-resistant epilepsy negatively influenced neurodevelopmental and adaptive functions. Conclusion Better understanding of the functional levels and profiles of neurodevelopment and psychological comorbidity in children with mitochondrial diseases in the prediagnostic period is essential for adequate support and QOL of children with mitochondrial diseases and their parents.
Eom S; Lee Y M
Pediatric Neurology
2017
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.pediatrneurol.2017.01.019" target="_blank" rel="noreferrer noopener">10.1016/j.pediatrneurol.2017.01.019</a>
Depression and anxiety symptoms in children and adolescents with autism spectrum disorders without intellectual disability
Prevalence; Comorbidity; Depression; Anxiety; Children; Adolescents; Autism; DEVELOPMENTAL; PSYCHIATRY; Psychology; ASPERGER-SYNDROME; At Risk Persons; Depression/psychology; DIAGNOSTIC INTERVIEW; Education; FRIENDSHIP; Intelligence Quotient; parent; People; PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; Rehabilitation; Special; Symptoms (Individual Disorders); VERSION
Recent studies have shown that rates of depression and anxiety symptoms are elevated among individuals with autism spectrum disorders (ASDs) of various ages and IQs and that depression/anxiety symptoms are associated with higher IQ and fewer ASD symptoms. In this study which examined correlates of depression and anxiety symptoms in the full school-age range of children and adolescents (age 6-18) with ASDs and IQs greater than or equal to 70 (n = 95), we also observed elevated rates of depression/anxiety symptoms, but we did not find higher IQ or fewer ASD symptoms among individuals with ASDs and depression or anxiety symptoms. These findings indicate an increased risk for depression/anxiety symptoms in children and adolescents with ASDs without intellectual disability, regardless of age, IQ, or ASD symptoms. (Contains 2 tables and 1 figure.)
Strang JF; Kenworthy L; Daniolos P; Case L; Wills MC; Martin A; Wallace GL
Research In Autism Spectrum Disorders
2012
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/j.rasd.2011.06.015" target="_blank" rel="noreferrer">10.1016/j.rasd.2011.06.015</a>