Alström Syndrome Presenting as Isolated Dilated Cardiomyopathy

Nerakh, Gayatri; Ranganath, Prajnya

doi:10.1007/s12098-018-2807-9

Cited by 10 publications

(17 citation statements)

References 8 publications

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“…Patients with AS rarely live >40 years ( 22 ). At present, there is no specific treatment for AS, but early diagnosis and intervention can alleviate the progress of the disease phenotypes and improve the survival period and quality of life of patients ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

A novel variant in ALMS1 in a patient with Alstr�m syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review

et al. 2020

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alström syndrome (aS) is a type of monogenic syndromic ciliopathy disease. The main clinical features of aS include cone-rod malnutrition, sensorineural hearing loss, metabolic dysfunctions and multiple organ failure, which are caused by mutations of alström syndrome protein 1 (ALMS1) gene. The current study aimed to identify pathogenic variants in a chinese patient with aS and to review the relevant literature. Genomic dna extracted from a 10-year-old male with aS was evaluated using a disease-targeted gene panel. according to the bioinformatics analysis, the current study identified a novel frameshift mutation in exon 8 (c.2988_2989del, p.T996fs) and a rare nonsense mutation in exon 10 (c.9535c>T, p.r3179*) of the ALMS1 gene. Both parents were heterozygous carriers of this gene. To the best of our knowledge, these mutations have not been reported in normal population databases. according to the criteria of the american college of Medical Genetics and Genomics, the mutations were pathogenic. Based on these findings, amniotic fluid sample was used for prenatal diagnosis of the couple's fetus, and it was observed that the fetus carried c.9535c>T, and not c.2988del. during the follow-up duration of >2 years of the fetus, it was confirmed that he was a healthy male. The results of the present study identified two compound heterozygous alMS1 mutations in a patient with the symptoms of alström syndrome and reported a novel alMS1 variant which expands the spectrum of alMS1 variants in aS.

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Section: Discussionmentioning

confidence: 99%

A novel variant in ALMS1 in a patient with Alstr�m syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review

et al. 2020

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“…Hearing loss is reported in 89% of patients with a mean age of onset of 5 years (Marshall et al, 2005). Other atypical presentations of ALMS have been reported and include a case of putative isolated cardiomyopathy in a 2-month old child followed up until the age of 4.5 months (Nerakh and Ranganath, 2019). The infant did, however, develop significant weight gain (>95th centile; +3 SD) in the short follow up period (up to 4.5 months) and no formal visual assessments were conducted (Nerakh and Ranganath, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Other atypical presentations of ALMS have been reported and include a case of putative isolated cardiomyopathy in a 2-month old child followed up until the age of 4.5 months (Nerakh and Ranganath, 2019). The infant did, however, develop significant weight gain (>95th centile; +3 SD) in the short follow up period (up to 4.5 months) and no formal visual assessments were conducted (Nerakh and Ranganath, 2019). In this case, molecular analysis confirmed two novel compound heterozygous truncating variations in ALMS1.…”

Section: Discussionmentioning

confidence: 99%

Atypical Retinal Phenotype in a Patient With Alström Syndrome and Biallelic Novel Pathogenic Variants in ALMS1, Including a de novo Variation

Mauring¹,

Porter

Pelletier³

et al. 2020

Front. Genet.

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Alström syndrome (ALMS) is a rare autosomal recessive multi-organ syndrome considered to date as a ciliopathy and caused by variations in ALMS1. Phenotypic variability is welldocumented, particularly for the systemic disease manifestations; however, early-onset progressive retinal degeneration affecting both cones and rods (cone-rod type) is universal, leading to blindness by the teenage years. Other features include cardiomyopathy, kidney dysfunction, sensorineural deafness, and childhood obesity associated with hyperinsulinemia and type 2 diabetes mellitus. Here, we present an unusual and delayed retinal dystrophy phenotype associated with ALMS in a 14-year-old female, with affected cone function and surprising complete preservation of rod function on serial electroretinograms (ERGs). High-throughput sequencing of the affected proband revealed compound heterozygosity with two novel nonsense variations in the ALMS1 gene, including one variant of de novo inheritance, an unusual finding in autosomal recessive diseases. To confirm the diagnosis in the context of an unusually mild phenotype and identification of novel variations, we demonstrated the biallelic status of the compound heterozygous variations (c.[286C > T];[1211C > G], p.[(Gln96 *)];[(Ser404 *)]). This unique case extends our knowledge of the phenotypic variability and the pathogenic variation spectrum in ALMS patients.

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“…Indeed, the phenotype of AS partly overlaps with that of the other main ciliopathy, Bardet-Biedl syndrome (BBS), and differential diagnosis is often made by excluding clinical manifestations specific to BBS [ 26 ]. Atypical cases with non-syndromic retinal dystrophy or isolated cardiomyopathy due to variants in ALMS1 have also been reported [ 27 , 28 ]. The development of high-throughput sequencing technologies, such as whole-genome or exome sequencing, offers an exceptionally valuable screening tool for obtaining clear genetic diagnoses and identifying disease-causing gene variants.…”

Section: Introductionmentioning

confidence: 99%

A very early diagnosis of Alstrӧm syndrome by next generation sequencing

Gatticchi

Miertuš²,

Maltese

et al. 2020

BMC Med Genet

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Background: Alström syndrome is a rare recessively inherited disorder caused by variants in the ALMS1 gene. It is characterized by multiple organ dysfunction, including cone-rod retinal dystrophy, dilated cardiomyopathy, hearing loss, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus and systemic fibrosis. Heterogeneity and agedependent development of clinical manifestations make it difficult to obtain a clear diagnosis, especially in pediatric patients. Case presentation: Here we report the case of a girl with Alström syndrome. Genetic examination was proposed at age 22 months when suspected macular degeneration was the only major finding. Next generation sequencing of a panel of genes linked to eye-related pathologies revealed two compound heterozygous variants in the ALMS1 gene. Frameshift variants c.1196_1202del, p.(Thr399Lysfs*11), rs761292021 and c.11310_11313del, (p.Glu3771Trpfs*18), rs747272625 were detected in exons 5 and 16, respectively. Both variants cause frameshifts and generation of a premature stop-codon that probably leads to mRNA nonsense-mediated decay. Validation and segregation of ALMS1 variants were confirmed by Sanger sequencing. Conclusions: Genetic testing makes it possible, even in childhood, to increase the number of correct diagnoses of patients who have ambiguous phenotypes caused by rare genetic variants. The development of high-throughput sequencing technologies offers an exceptionally valuable screening tool for clear genetic diagnoses and ensures early multidisciplinary management and treatment of the emerging symptoms.

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Alström Syndrome Presenting as Isolated Dilated Cardiomyopathy

Cited by 10 publications

References 8 publications

A novel variant in ALMS1 in a patient with Alstr�m syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review

A novel variant in ALMS1 in a patient with Alstr�m syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review

Atypical Retinal Phenotype in a Patient With Alström Syndrome and Biallelic Novel Pathogenic Variants in ALMS1, Including a de novo Variation

A very early diagnosis of Alstrӧm syndrome by next generation sequencing

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