1. Ramocki MB, Peters SU, Tavyev YJ, Zhang F, Carvalho CM, Schaaf CP, Richman R, Fang P, Glaze DG, Lupski JR, Zoghbi HY. {{Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome}}. {Ann Neurol}. 2009 Mar 26;66(6):771-82.
OBJECTIVE: There have been no objective assessments to determine whether boys with MECP2 duplication have autism or whether female carriers manifest phenotypes. This study characterizes the clinical and neuropsychiatric phenotypes of affected boys and carrier females. METHODS: Eight families (9 males and 9 females) with MECP2 duplication participated. A detailed history, physical examination, electroencephalogram, developmental evaluation, Autism Diagnostic Observation Schedule, and Autism Diagnostic Interview-Revised were performed for each boy. Carrier females completed the Symptom Checklist-90-R, Wechsler Abbreviated Scale of Intelligence, Broad Autism Phenotype Questionnaire, and detailed medical and mental health histories. Size and gene content of each duplication were determined by array comparative genome hybridization. X-chromosome inactivation patterns were analyzed using leukocyte DNA. MECP2 and IRAK1 RNA levels were quantified from lymphoblast cell lines, and western blots were performed to assess MeCP2 protein levels. RESULTS: All of the boys demonstrated mental retardation and autism. Poor expressive language, gaze avoidance, repetitive behaviors, anxiety, and atypical socialization were prevalent. Female carriers had psychiatric symptoms, including generalized anxiety, depression, and compulsions that preceded the birth of their children. The majority exhibited features of the broad autism phenotype and had higher nonverbal compared to verbal reasoning skills. INTERPRETATION: Autism is a defining feature of the MECP2 duplication syndrome in boys. Females manifest phenotypes despite 100% skewing of X-inactivation and normal MECP2 RNA levels in peripheral blood. Analysis of the duplication size, MECP2 and IRAK1 RNA levels, and MeCP2 protein levels revealed that most of the traits in affected boys are likely due to the genomic region spanning of MECP2 and IRAK1. The phenotypes observed in carrier females may be secondary to tissue-specific dosage alterations and require further study. Ann Neurol 2009;66:771-782.
2. Tanaka M, Nakanishi K, Sugimoto Y, Misawa H, Takigawa T, Nishida K, Ozaki T. {{Computer navigation-assisted spinal fusion with segmental pedicle screw instrumentation for scoliosis with rett syndrome:a case report}}. {Acta Med Okayama}. 2009 Dec;63(6):373-7.
Scoliosis is a common clinical manifestation of Rett syndrome, a neurodevelopmental disorder that almost exclusively affects females. The spinal curve in patients with Rett syndrome is typically a long C curve of a neuromuscular type. As the onset of the scoliosis is very early and shows rapid progression, early surgical intervention has been recommended to prevent a life-threatening collapsing spine syndrome. However, there are high perioperative risks in Rett syndrome patients who undergo spinal surgery, such as neurological compromise and respiratory dysfunction due to rigid spinal curve. We herein report the surgical result of treating severe rapid progressive thoracic scoliosis in a 16-year-old girl with Rett syndrome. Posterior segmental pedicle screw fixation was performed from T1 to L3 using a computer-assisted technique. Post-operative radiography demonstrated a good correction of the curve in both the sagittal and coronal alignment. There were no postoperative complications such as neurological compromise. The patient had maintained satisfactory spinal balance as of the 3-year follow-up examination.
3. Voituron N, Zanella S, Menuet C, Lajard AM, Dutschmann M, Hilaire G. {{Early abnormalities of post-sigh breathing in a mouse model of Rett Syndrome}}. {Respir Physiol Neurobiol}. 2009 Dec 26.
Rett syndrome is a neurodevelopmental disease accompanied by complex, disabling symptoms, including breathing symptoms. Because Rett syndrome is caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2), Mecp2-deficient mice have been generated as experimental model. Males of Mecp2-deficient mice (Mecp2(-/y)) breathe normally at birth but show abnormal respiratory responses to hypoxia and hypercapnia from postnatal day 25 (P25). After P30, Mecp2(-/y) mice develop breathing symptoms reminiscent of Rett syndrome, aggravating until premature death at around P60. Using plethysmography, we analyzed the sighs and the post-sigh breathing pattern of unrestrained wild type male mice (WT) and Mecp2(-/y) mice from P15 to P60. Sighs are spontaneous large inspirations known to prevent lung atelectasis and to improve alveolar oxygenation. However, Mecp2(-/y) mice show early abnormalities of post-sigh breathing, with long-lasting post-sigh apnoeas, reduced tidal volume when eupnoea resumes and lack of post-sigh bradypnoea which develop from P15, aggravate with age and possibly contribute to breathing symptoms to come.
