PPP2R5D-Related Neurodevelopmental Disorder or Developmental and Epileptic Encephalopathy?: A Novel Phenotypic Description and Review of Published Cases

2021 ◽  
Author(s):  
Priyanka Madaan ◽  
Amrit Kaur ◽  
Lokesh Saini ◽  
Pradip Paria ◽  
Sameer Vyas ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Case Reports ◽  
Neurodevelopmental Disorder ◽  
Epileptic Encephalopathy ◽  
Regulatory Subunit ◽  
History Of ◽  
The Common ◽  
Diagnostic Clue ◽  
Protein Phosphatase 2 ◽  
Subunit B

Abstract Background Protein phosphatase 2 regulatory subunit B′ delta (PPP2R5D)-related neurodevelopmental disorder is caused by pathogenic variations in the PPP2R5D gene, product of which is involved in dephosphorylation. This is a rare disorder with description limited to case reports. Its phenotypic spectrum has expanded over the last decade. Methods We report a child with a developmental and epileptic encephalopathy phenotype with a pathogenic PPP2R5D variant. This phenotype has not been previously reported. We also reviewed the previously published reports of patients with this disorder. Results Including the index child, 28 cases (15 girls) were identified from nine relevant research items for analysis. All patients had developmental delay. History of seizures was observed in seven patients while macrocephaly was seen in nearly 80% of patients. Nonneurological manifestations were observed in 13 patients with the most common one being ophthalmological manifestations. The most common genetic variation was c.G592A (p.E198K). The common phenotypic associations of this variation were developmental delay, macrocephaly (11/15), and epilepsy (6/15). Conclusion PPP2R5D gene variations should be suspected in children with developmental delay, autistic features, macrocephaly with or without epilepsy in the absence of any clear etiology. Dysmorphic features might provide a diagnostic clue. DEE phenotype may also be the presenting feature and might be an underreported entity.

Fulminant varicella hepatitis: a rare but lethal cause of abdominal pain

2021 ◽  
Vol 14 (9) ◽  
pp. e244081
Author(s):  
Christopher Fang ◽  
Junice Wong ◽  
Wei Wen Ang
Keyword(s):  
Abdominal Pain ◽  
Hepatitis A ◽  
Case Reports ◽  
Antibody Testing ◽  
Salient Points ◽  
Vesicular Rash ◽  
History Of ◽  
Laboratory Investigations ◽  
The Common ◽  
Upper Abdominal

An 81-year-old woman with no history of immunocompromise presented with 2 days of upper abdominal pain associated with nausea. On arrival, her physical examination was unremarkable apart from mild epigastric and right hypochondriac tenderness, and laboratory investigations were unremarkable apart from mild thrombocytopenia and transaminitis. A CT scan performed on the day of admission revealed a tiny 0.3 cm stone in the common bile duct, with no upstream dilatation. On day 2 of admission, she developed a vesicular rash and with acutely worsening transaminitis. She deteriorated rapidly and demised from complications of acute liver failure within the next 24 hours. The diagnosis of varicella was confirmed with antibody testing. Fulminant varicella hepatitis is an extremely rare and lethal condition with only a handful of reported cases in the current literature. We aim to share our clinical experience and summarise the salient points from existing case reports.

Clinical Characteristics and Genotype–Phenotype Correlation in Children with KMT2E Gene-Related Neurodevelopmental Disorders: Report of Two New Cases and Review of Published Literature

2020 ◽  
Author(s):  
Indar Kumar Sharawat ◽  
Prateek Kumar Panda ◽  
Lesa Dawman
Keyword(s):  
Developmental Delay ◽  
Neurodevelopmental Disorder ◽  
Copy Number Variants ◽  
Cerebral White Matter ◽  
Global Developmental Delay ◽  
Missense Mutations ◽  
Search Terms ◽  
Pathogenic Factors ◽  
The Common ◽  
Variable Combination

Abstract Background In recent years, many new candidate genes are being identified as putative pathogenic factors in children with developmental delay and autism. Recently, heterozygous mutations in the KMT2E gene have been identified as a cause of a unique neurodevelopmental disorder with variable combination of global developmental delay or isolated speech delay, intellectual disability, autistic features, and seizures. Methods Here, we present two new cases of KMT2E mutation-associated neurodevelopmental disorder in a 4-year-old girl and 5-year-old boy. We also performed a pooled review of the previously published cases of KMT2E-related neurodevelopmental disorder. Articles were identified through search engines using appropriate search terms. Results Along with the presented 2 cases, 40 cases were analyzed. Out of them, 30, 6, and 4 children had protein-truncating mutations, missense mutations, and copy number variants, respectively. The common features were global developmental delay (97%) followed by macrocephaly (35%), seizures (30%), and autism (25%). Children with missense variants had severe phenotype, with microcephaly, profound developmental delay, and increased frequency of seizures. Neuroimaging revealed nonspecific changes, including cerebral white matter signal abnormalities. Conclusion KMT2E-related neurodevelopmental disorder remains one of the clinical differentials in children with global developmental delay and/or autistic features/seizure. With the reporting of more cases in the future, the already heterogeneous clinical spectrum of this disease is likely to be widened.

A case of palmar hypopigmentation induced by capecitabine in a gastrointestinal cancer patient

2021 ◽  
pp. 107815522110279
Author(s):  
Julian Gratiaux ◽  
Chloé Gossery ◽  
Chirine Rezzag-Mahcene ◽  
Damien Botsen ◽  
Laetitia Visseaux ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Adverse Drug Reaction ◽  
Case Reports ◽  
Antineoplastic Agent ◽  
Skin Lesions ◽  
Severe Adverse Effect ◽  
Gastrointestinal Cancers ◽  
History Of ◽  
The Common ◽  
Cutaneous Adverse Drug Reaction

Introduction Capecitabine is an antimetabolite antineoplastic agent widely used in the treatment gastrointestinal cancers. The common frequently reported cutaneous adverse drug reaction associated with capecitabin are a palmar-plantar erythrodysesthesia syndrome, rash and hyperpigmentation. This case reports a capecitabine-induced palmar hypopigmentation. Case report We report the case of a 74-years old patient with jejunum adenocarcinoma treated by capecitabine. The patient developed a pseudo-vitiligo after 2 cycles capecitabine and without history of cutaneous disorders. The skin lesions were characterized with skin hypopigmentation on both hands. Management and outcome: The hypopigmentation slowly recovered after capecitabine discontinuation. Conclusion This is the first described case of pseudo-vitiligo induced by capecitabine. This impressive but non-severe adverse effect should be known by oncologists and oncology pharmacists to reassure the patients in particular about the possible recovery after discontinuation of capecitabine.

scholarly journals Spectrum of Movement Disorders in GNAO1 Encephalopathy: in-depth Phenotyping and Literature Review

2020 ◽  
Author(s):  
Soo Yeon Kim ◽  
YoungKyu Shim ◽  
Young Joon Ko ◽  
Soojin Park ◽  
Se Song Jang ◽  
...  
Keyword(s):  
Literature Review ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Epileptic Encephalopathy ◽  
Global Developmental Delay ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Background GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations. Results Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Mean follow-up duration was 39 months (range, 7–78 months) and age at last examination was 8.0 years (range, 3.3–16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at 20 months of age on average (range, 0–75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patient’s mother who had mosaic variant. Distinct phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review. Conclusions We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.

scholarly journals Spectrum of Movement Disorders in GNAO1 Encephalopathy: In-Depth Phenotyping and Case-by-Case Analysis

2020 ◽  
Author(s):  
Soo Yeon Kim ◽  
YoungKyu Shim ◽  
Young Joon Ko ◽  
Soojin Park ◽  
Se Song Jang ◽  
...  
Keyword(s):  
Literature Review ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Epileptic Encephalopathy ◽  
Global Developmental Delay ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Background: GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations.Results: Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Median follow-up duration was 41 months (range, 7–78 months) and age at last examination was 7.4 years (range, 3.3–16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at median age of 3 months (range, 0–75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patient’s mother who had mosaic variant. Distinct and characteristics movement phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review. Conclusions: We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.

scholarly journals Protein phosphatase 2 regulatory subunit B''Alpha silencing inhibits tumor cell proliferation in liver cancer

2019 ◽  
Vol 8 (18) ◽  
pp. 7741-7753 ◽  
Author(s):  
Huijuan Chen ◽  
Jing Xu ◽  
Peixiao Wang ◽  
Qingming Shu ◽  
Lihong Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Tumor Cell ◽  
Protein Phosphatase ◽  
Regulatory Subunit ◽  
Tumor Cell Proliferation ◽  
Protein Phosphatase 2 ◽  
Subunit B

scholarly journals Spectrum of movement disorders in GNAO1 encephalopathy: in-depth phenotyping and case-by-case analysis

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Soo Yeon Kim ◽  
YoungKyu Shim ◽  
Young Joon Ko ◽  
Soojin Park ◽  
Se Song Jang ◽  
...  
Keyword(s):  
Literature Review ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Epileptic Encephalopathy ◽  
Global Developmental Delay ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Background GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations. Results Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Median follow-up duration was 41 months (range 7–78 months) and age at last examination was 7.4 years (range 3.3–16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at median age of 3 months (range 0–75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patient’s mother who had mosaic variant. Distinct and characteristics movement phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review. Conclusions We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.

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