Scoliosis in RETT Syndrome

Menachem, Shay; Hershkovich, Oded; Ackshota, Nissim; Friedlander, A.; Givon, Uri; Ben‐Zeev, Bruria; Caspi, Israel

doi:10.1097/bsd.0000000000001381

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…About half of patients develop scoliosis in adolescence, and approximately 20% of those cases require surgical correction. ( Killian et al, 2017 ; Rodocanachi Roidi et al, 2022 ; Menachem et al, 2023 ). Scoliosis is correlated with a more severe clinical presentation.…”

Section: Introductionmentioning

confidence: 99%

MECP2-related disorders while gene-based therapies are on the horizon

Allison,

Maletic-Savatic,

Pehlivan

2024

Front. Genet.

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The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities. This creates exciting opportunities for research and treatment development, and a few genetic disorders (e.g., spinal muscular atrophy) have recently been treated with gene-based therapies. MECP2 is found on the X chromosome and regulates the transcription of thousands of genes. Loss of MECP2 gene product leads to Rett Syndrome, a disease found primarily in females, and is characterized by developmental regression, motor dysfunction, midline hand stereotypies, autonomic nervous system dysfunction, epilepsy, scoliosis, and autistic-like behavior. Duplication of MECP2 causes MECP2 Duplication Syndrome (MDS). MDS is found mostly in males and presents with developmental delay, hypotonia, autistic features, refractory epilepsy, and recurrent respiratory infections. While these two disorders share several characteristics, their differences (e.g., affected sex, age of onset, genotype/phenotype correlations) are important to distinguish in the light of gene-based therapy because they require opposite solutions. This review explores the clinical features of both disorders and highlights these important clinical differences.

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Section: Introductionmentioning

confidence: 99%

MECP2-related disorders while gene-based therapies are on the horizon

Allison,

Maletic-Savatic,

Pehlivan

2024

Front. Genet.

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“…Disease burden in RTT is primarily driven by the lack of a cure for the disorder, although approved targeted therapies (e.g., Trofinetide) and symptomatic treatments (e.g., antiepileptics) can improve clinical presentation [5][6][7]. Additional symptoms can be managed through surgical interventions, including spinal fusion to correct scoliosis and gastronomy tube placement to address feeding concerns common among individuals with RTT [8,9]. While these interventions are effective in their own domains, they do not cure nor resolve the molecular basis of the disorder.…”

Section: Introductionmentioning

confidence: 99%

Normalized Clinical Severity Scores Reveal a Correlation between X Chromosome Inactivation and Disease Severity in Rett Syndrome

Merritt,

Fang,

Caylor

et al. 2024

Genes

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Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI), resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age-dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity, allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

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