Co-occurrence of Metachromatic Leukodystrophy in Phelan-McDermid Syndrome

Mingbunjerdsuk, Dararat; Wong, Melissa H.; Bozarth, Xiuhua; Sun, Angela

doi:10.1177/0883073820960308

Cited by 5 publications

(5 citation statements)

References 17 publications

(17 reference statements)

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“…Examples include metachromatic leukodystrophy (MLD; ARSA defect) and megalencephalic leukoencephalopathy with subcortical cysts (MLC; MLC1 defect). There are a few case reports of individuals with PMS and MLD who presented with progressive neurological deterioration (Ahn et al, 2020; Bisgaard et al, 2009; Mingbunjerdsuk et al, 2021). Because patients with presymptomatic or early‐stage MLD may be candidates for hematopoietic stem cell transplantation, some authors suggest MLD screening with urine sulfatides at the time of diagnosis of PMS associated with a deletion including ARSA (Mingbunjerdsuk et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Section: Diagnostic Testingmentioning

confidence: 99%

“…Because patients with presymptomatic or early-stage MLD may be candidates for hematopoietic stem cell transplantation, some authors suggest MLD screening with urine sulfatides at the time of diagnosis of PMS associated with a deletion including ARSA (Mingbunjerdsuk et al, 2021).…”

Section: Diagnostic Testingmentioning

confidence: 99%

See 2 more Smart Citations

Updated consensus guidelines on the management of Phelan–McDermid syndrome

Srivastava,

Sahin,

Buxbaum

et al. 2023

American J of Med Genetics Pt A

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Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and largescale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The For affiliations refer to page 2038

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Section: Resultsmentioning

confidence: 99%

Section: Diagnostic Testingmentioning

confidence: 99%

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Updated consensus guidelines on the management of Phelan–McDermid syndrome

Srivastava,

Sahin,

Buxbaum

et al. 2023

American J of Med Genetics Pt A

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“…Causes for regressive symptoms represent psychiatric disorders like schizophrenia, depression, and bipolar disorder [3,4] that should be assessed by standard neuropsychological evaluation [5]. Additional triggers for regression include a comorbid a comorbid metachromatic leukodystrophy in cases of impairment of the ARSA gene on chromosome 22 [6] that should be taken into account when the MRI shows typical abnormalities that go along with this metabolic disease.…”

Section: Discussionmentioning

confidence: 99%

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

Jesse

Delling

Schön

et al. 2021

IJMS

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Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the SHANK3 gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. SHANK3 is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation. Individuals with PMcD present with intellectual disability, muscular hypotonia, and severely delayed or absent speech. Further neuropsychiatric manifestations cover symptoms of the autism spectrum, epilepsy, bipolar disorders, schizophrenia, and regression. Regression is one of the most feared syndromes by relatives of PMcD patients. Current scientific evidence indicates that the onset of regression is variable and affects language, motor skills, activities of daily living and cognition. In the case of regression, patients normally undergo further diagnostics to exclude treatable reasons such as complex-focal seizures or psychiatric comorbidities. Here, we report, for the first time, the case of a young female who developed progressive symptoms of regression and a dystonic-spastic hemiparesis that could be traced back to a comorbid multiple sclerosis and that improved after treatment with methylprednisolone.

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“…A pathogenic nucleotide variant in this critical gene can also cause PMS (3). It is characterized by different clinical symptoms with varying degrees of severity, such as severe speech retardation, neonatal hypotension, Intellectual Disability or impairment, intellectual disability (ID), autism spectrum disorder (ASD), seizures, heart defects, recurrent upper respiratory tract infections, gastroesophageal reflux and metachromatic leukodystrophy (4)(5)(6)(7). Until now, the true prevalence of PMS is unclear for us, according to the data from the Foundation of PMS, more than 2,000 people have been diagnosed with PMS worldwide.…”

Section: Introductionmentioning

confidence: 99%

Phelan–McDermid Syndrome in Pediatric Patients With Novel Mutations: Genetic and Phenotypic Analyses

Chen

Yao²,

Wu³

et al. 2022

Front. Pediatr.

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BackgroundPhelanrMcDermid syndrome (PMS) is an uncommon autosomal dominant inherited developmental disorder. The main characteristics are hypotonia, intellectual disability, autism spectrum disorder, autism-like behaviors and tiny facial deformities. Most cases are caused by the deletion of the 22q13 genomic region, including the deletion of SHANK3.MethodsGenetic and phenotype evaluations of ten Chinese pediatric patients were performed. The clinical phenotypes and genetic testing results were collected statistically. We analyzed the deletion of the 22q13 genomic region and small mutations in SHANK3 (GRCh37/hg19) and performed parental genotype verification to determine whether it was related to the parents or was a novel mutation.ResultsThe age of the patients diagnosed with PMS ranged from 0 to 12 years old. Nine of the pediatric patients experienced Intellectual Disability, language motion development delay and hypotonia as prominent clinical features. One subject had autism, two subjects had abnormal electroencephalogram discharge and one subject was aborted after fetal diagnosis. Three patients had a SHANK3 mutation or deletion. All but the aborted fetuses had intellectual disability. Among the ten patients, a deletion in the 22q13 region occurred in seven patients, with the smallest being 60.6 kb and the largest being >5.5 Mb. Three patients had heterozygous mutations in the SHANK3 gene.ConclusionAll ten patients had novel mutations, and three of these were missense or frameshift mutations. For the first time reported, it is predicted that the amino acid termination code may appear before protein synthesis. The novel mutations we discovered provide a reference for clinical research and the diagnosis of PMS.

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Co-occurrence of Metachromatic Leukodystrophy in Phelan-McDermid Syndrome

Cited by 5 publications

References 17 publications

Updated consensus guidelines on the management of Phelan–McDermid syndrome

Updated consensus guidelines on the management of Phelan–McDermid syndrome

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

Phelan–McDermid Syndrome in Pediatric Patients With Novel Mutations: Genetic and Phenotypic Analyses

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