Hepatoblastoma in a male with <i>MECP2</i> duplication syndrome

Trobaugh‐Lotrario, Angela D.; Martin, Judith A.; López‐Terrada, Dolores

doi:10.1002/ajmg.a.37474

Cited by 8 publications

(6 citation statements)

References 20 publications

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“…Gastroesophageal reflux with subsequent aspiration was suggested as a cause for frequent respiratory tract infections [27,58]. However, only 55% (149/270) of the patients were described to suffer from reflux whereas 78% of the patients (376/479) were described to suffer from recurrent or severe infections ( [3,5,6,9,15,18,23,24,26,27,29,30,[33][34][35]37,39,42,46,47,49,56,58,[71][72][73][74][75][76], Table 1).…”

Section: Discussionmentioning

confidence: 99%

IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation

Gottschalk

Kölsch

Wagner

et al. 2022

Preprint

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Purpose Besides their developmental and neurological phenotype, most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death. Standardized pneumological diagnostics, targeted anti-infectious treatment and knowledge of the underlying pathomechanism that triggers strong inflammation are unmet clinical needs. We investigated the influence of IRAK1 overexpression on the canonical NF-κB signaling as a possible cause for excessive inflammation in these patients. Methods NF-κB signaling was examined by measuring the production of proinflammatory cytokines as well as evaluating the IRAK1 phosphorylation and degradation as well as the IκBα-degradation upon stimulation with IL-1β and TLR-agonists in SV40 immortalized fibroblasts, PBMCs and whole blood of 9 patients with MECP2/IRAK1 duplication syndrome, respectively. Results Both, MECP2/IRAK1-duplicated patients and healthy controls, showed similar production of IL-6 and IL-8 upon activation with IL-1β and TLR4/2/6-agonists in immortalized fibroblasts, PBMCs and whole blood. Patients and controls have equivalent patterns of IRAK1 phosphorylation and degradation as well as IκBα degradation upon stimulation with IL-1β. Conclusion Patients with MECP2/IRAK1 duplication syndrome do not show increased canonical NF-κB signaling in immortalized fibroblasts, PBMCs and whole blood. Therefore, we assume that these patients do not benefit from a therapeutic suppression of this pathway.

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Section: Discussionmentioning

confidence: 99%

IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation

Gottschalk

Kölsch

Wagner

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Resultant hypoxemia may occur [ 72 ], and as such individuals may require oxygen supplementation [ 82 ], or ventilatory support [ 13 ]. Respiratory infections such as pneumonia, bronchitis and bronchiolitis have been reported in almost three-quarters (n = 367) of 498 individuals from 60 studies (Table 5 ) [ 1 – 4 , 8 – 10 , 12 – 14 , 16 – 22 , 24 – 32 , 34 – 38 , 40 – 48 , 51 – 53 , 55 – 57 , 59 – 64 , 66 – 74 , 76 – 78 , 81 – 86 ], often resulting in frequent hospitalisation [ 8 , 17 , 64 , 73 , 76 , 77 , 81 , 84 ]. Antibiotic therapy is commonly required to manage respiratory infections [ 72 , 81 ], with severe presentations often resulting in multi-disciplinary management including immunoglobulin replacement [ 72 ], airway clearance therapy/devices [ 72 , 78 ], and ventilatory support [ 28 , 52 , 57 , 64 , 76 ].…”

Section: The Syndromic Phenotype Of Mecp2 Duplicat...mentioning

confidence: 99%

“…It has been recommended that botulinum toxin be a considered treatment for contractures and to prevent joint dislocations [ 25 , 30 ]. Less common musculoskeletal problems such as juvenile idiopathic arthritis [ 67 ], osteopenia/osteoporosis [ 66 , 85 ], joint luxations/subluxations [ 40 , 43 ], joint hypermobility [ 7 , 26 , 27 , 55 ], muscular atrophy [ 1 ], lordosis [ 28 ], and torticollis [ 32 , 40 ] have also been reported. Fractures have been reported [ 17 , 32 , 66 , 77 ], however further research is required to confirm the prevalence and underlying mechanisms.…”

Section: The Syndromic Phenotype Of Mecp2 Duplicat...mentioning

confidence: 99%

A brief history of MECP2 duplication syndrome: 20-years of clinical understanding

Downs

Baynam

et al. 2022

Orphanet J Rare Dis

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MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene—a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000. The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features—although these comorbidities are not yet understood with sufficient granularity. This review has covered the past two decades of MDS case studies and series since the discovery of the disorder in 1999. After comprehensively reviewing the reported characteristics, this review has identified areas of limited knowledge that we recommend may be addressed by better phenotyping this disorder through an international data collection. This endeavour would also serve to delineate the clinical overlap between MDS and RTT.

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“…Contractures of the ankle, knees, hip/trunk, elbows and wrist joints have also been reported [ 19 – 24 ]. Less common musculoskeletal problems are also present, such as juvenile idiopathic arthritis [ 25 ], osteopenia/osteoporosis [ 26 , 27 ], joint hypermobility [ 28 – 31 ], muscle atrophy [ 32 ], lordosis [ 33 ] and torticollis [ 34 , 35 ]. Skeletal deformations were also found, especially in patients with more severe mutations (e.g.…”

Section: Introductionmentioning

confidence: 99%

Pain in Rett syndrome: a pilot study and a single case study on the assessment of pain and the construction of a suitable measuring scale

Fabio

Chiarini

Canegallo

2022

Orphanet J Rare Dis

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Background Rett Syndrome (RTT) is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births. Severe physical, language, and social impairments impose a wide range of limitations in the quality of life of the patients with RTT. Comorbidities of patients with RTT are varied and cause a lot of pain, but communicating this suffering is difficult for these patients due to their problems, such as apraxia that does not allow them to express pain in a timely manner, and their difficulties with expressive language that also do not permit them to communicate. Two studies, a pilot study and a single case study, investigate the manifestation of pain of patients with RTT and propose a suitable scale to measure it. Aims of this study The first aim was to describe pain situations of RTT by collecting information by parents; the second aim was to test and compare existing questionnaires for non-communicating disorders on pain such as Pain assessment in advanced demenzia (PAINAD), the Critical care pain observation tool (CPOT) and the Non-communicating Children’s Pain Checklist-Revised (NCCPC-R) to assess which of them is best related to the pain behavior of patients with RTT. The third aim was to identify the specific verbal and non-verbal behaviors that characterize pain in girls with Rett syndrome, discriminating them from non-pain behaviors. Method Nineteen participants, eighteen girls with RTT and one girl with RTT with 27 manifestations of pain were video-recorded both in pain and base-line conditions. Two independent observers codified the 90 video-recording (36 and 54) to describe their behavioral characteristics. Results The two studies showed that the most significant pain behaviors expressed by girls with respect to the baseline condition, at the facial level were a wrinkled forehead, wide eyes, grinding, banging teeth, complaining, making sounds, crying and screaming, and the most common manifestations of the body were tremors, forward and backward movement of the torso, tension in the upper limbs, increased movement of the lower limbs and a sprawling movement affecting the whole body. Conclusion The results of the two studies helped to create an easy-to-apply scale that healthcare professionals can use to assess pain in patients with Rett’s syndrome. This scale used PAINAD as its basic structure, with some changes in the items related to the behavior of patients with RTT.

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Hepatoblastoma in a male with MECP2 duplication syndrome

Cited by 8 publications

References 20 publications

IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation

IRAK1 Duplication in MECP2 Duplication Syndrome Does Not Increase Canonical NF-κB-Induced Inflammation

A brief history of MECP2 duplication syndrome: 20-years of clinical understanding

Pain in Rett syndrome: a pilot study and a single case study on the assessment of pain and the construction of a suitable measuring scale

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