Molecular Syndromology最新文献

{"title":"First Reported Co-Occurrence of Bardet-Biedl Syndrome Type 10 and Autism Spectrum Disorder: A Case Report and Clinical Review.","authors":"Ahmet Güleç, Hamide Betul Gerik-Celebi","doi":"10.1159/000547413","DOIUrl":"10.1159/000547413","url":null,"abstract":"<p><strong>Introduction: </strong>Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, multisystemic ciliopathy, whereas autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and restricted, repetitive behaviors. While both conditions are independently associated with genetic etiologies, their co-occurrence is exceptionally rare. To date, no prior report has confirmed such co-occurrence through molecular genetic analysis.</p><p><strong>Case presentation: </strong>We report a 4-year-old male diagnosed with both BBS type 10 and ASD. Whole exome sequencing (WES) revealed a homozygous pathogenic variant in the <i>BBS10</i> gene and a novel heterozygous intronic variant in the <i>OGT</i> gene, classified as a variant of uncertain significance. Clinically, the patient exhibited features consistent with both disorders, including retinal degeneration, polydactyly, renal anomalies, hypotonia, and ASD-specific behavioral patterns.</p><p><strong>Conclusion: </strong>This case represents the first genetically confirmed co-occurrence of BBS10 and ASD. The identification of a potentially contributory non-coding variant in the <i>OGT</i> gene provides novel insight into the shared genetic and pathophysiological mechanisms underlying ciliopathies and neurodevelopmental disorders. The findings emphasize the importance of dual diagnostic consideration in complex pediatric cases and demonstrate the value of genomic analysis in revealing rare genetic overlaps.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"264-270"},"PeriodicalIF":0.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Hyperekplexia Caused by a Novel Homozygous <i>SLC6A5</i> Variant: A Case Report.","authors":"Fatma Hilal Yılmaz, Ayça Burcu Kahraman, Fahrettin Duymuş, Hatice Koçak Eker, Halil Çelik, Melek Büyükeren, Beyza Özcan, Ramazan Keçeci","doi":"10.1159/000547752","DOIUrl":"10.1159/000547752","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperekplexia is a rare non-epileptic paroxysmal disorder characterized by a marked startle response and hypertonia to auditory, tactile, or visual sudden external stimuli. <i>GLRA1</i>, <i>SLC6A5</i>, <i>GLRB</i>, and <i>ATAD1</i> gene pathogenic variants have been identified in these patients.</p><p><strong>Case report: </strong>The girl was born 39+1 weeks and admitted to the neonatal intensive care unit with spasm-like contractions and followed by breath holding. Except for transient hyperammonemia, neurologic and metabolic tests were normal, and there was no seizure-like movement during hospitalization. In the 4th month of her life, the patient had spasm-like findings with stimulation, and the symptoms were controlled with clonazepam, considering hyperekplexia. Clinical exome sequencing revealed a previously undescribed homozygous variant [c.748T>C; p.(Ser250Pro) in exon 4] in the <i>SLC6A5</i> (NM_004211.5) gene. Sanger sequencing confirmed the c.748T>C variant in the family: both parents were heterozygous carriers, while the brother was homozygous. Her sibling also had stimulus-induced crying and stiffness in infancy, but these resolved within months without treatment, and his developmental milestones have been age-appropriate.</p><p><strong>Conclusions: </strong>This case highlights the importance of recognizing hereditary hyperekplexia in the differential diagnosis of neonatal seizures and supports the potential pathogenic relevance of the <i>SLC6A5</i> c.748T>C (p.Ser250Pro) variant, particularly in benign, nonrecurrent cases with transient hyperammonemia from catabolic stress and glycine transporter dysfunction.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"271-275"},"PeriodicalIF":0.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic and Phenotypic Characteristics of Turkish Patients with Sjögren-Larsson Syndrome.","authors":"Suzan İcil, Mustafa Kılıç, Esra Sayar, Abdullah Sezer","doi":"10.1159/000548337","DOIUrl":"10.1159/000548337","url":null,"abstract":"<p><strong>Introduction: </strong>Sjögren-Larsson syndrome (SLS) (OMIM #270200) is an autosomal recessively inherited lipid disorder caused by pathogenic variants in <i>ALDH3A2</i> gene encoding the fatty aldehyde dehydrogenase (FALDH) enzyme, that catalyzes the oxidation of fatty aldehyde to fatty acid. It is a rare neurocutaneous disorder characterized by the triad of congenital ichthyosis, spasticity, and intellectual disability. The aim of study was to investigate phenotypic and molecular characteristics of Turkish patients with SLS.</p><p><strong>Methods: </strong>Literature search was performed by entering the keywords <i>ALDH3A2</i>, FALDH, SLS in TR index journal list in Turkish and PubMed in English. Turkish patients with SLS reported up to date were retrospectively analyzed.</p><p><strong>Results: </strong>A total of 58 patients from 36 unrelated Turkish families were included in this study. Consanguinity was present in 73% of families. All but three patients younger than 18 months exhibited the triad of ichthyosis, developmental delay, and spastic di-/tetraplegia. Ophthalmological abnormalities were observed in 45% of patients, prematurity in 30%, epilepsy in 28%, and scoliosis in 17%. Additionally, only 2% of patients had peripheral neuropathy. Abnormal findings on brain imaging studies were detected in 84% of patients, all of whom demonstrated white matter involvement, while cerebral atrophy was present in 10%. All families had homozygous mutations, with missense in 45%, nonsense/frameshift/deletion in 35%, and splicing in 20%. Among the 15 distinct variants identified, only three, c.683G>A p.(Arg228His), c.24_25delinsTT p.(Arg9*), and c.1108-1G>C, were found to be recurrent. A review of the literature suggests that the c.24_25delinsTT p.(Arg9*) variant may be specific to the Turkish population, whereas the c.683G>A p.(Arg228His) variant appears to have a broader regional distribution across the Middle East.</p><p><strong>Conclusion: </strong>Although mild and severe phenotypes have been reported, the classical triad plays an important role in the preliminary diagnosis. Phenotypic findings were similar, but genotypic diversity was remarkable, and no clear genotype-phenotype correlation was observed. To make population-specific inferences, it is necessary to generate data from a larger patient cohort with haplotype analysis.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"17 3","pages":"238-254"},"PeriodicalIF":0.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down Syndrome: From Pregnancy through Childhood in Türkiye.","authors":"Elif Yilmaz Gulec, Sena Cetin, Mustafa Gunes, Alper Gezdirici","doi":"10.1159/000548225","DOIUrl":"10.1159/000548225","url":null,"abstract":"<p><strong>Introduction: </strong>Down syndrome is the most common genetic cause of multiple congenital malformations and intellectual disability. The prevalence of the disorder and accompanying malformations, prenatal and postnatal features, and clinical approach to the syndrome vary across different regions worldwide. This study aims to share our clinic's experience with Down syndrome from pregnancy through childhood from a medical geneticist's perspective and to summarize the prenatal and postnatal characteristics of our patients.</p><p><strong>Methods: </strong>A 10-year review of medical records was conducted for patients with Down syndrome who were followed between 2010 and 2021. Patient data including sex, karyotype, follow-up period, age at first and last visit, congenital malformations, organic disorders, prenatal screening data, neonatal history, neuromotor developmental milestones, and growth parameters were evaluated.</p><p><strong>Results: </strong>Overall, 324 children with Down syndrome were evaluated. Overall, 95% (308) had regular trisomy 21. The mean age at admission was 6.09 ± 1.99 months, and patients were followed for an average of 32.7 ± 3.97 months. Overall, 51% of neonates and 53.5% overall were hospitalized. While common disorders such as congenital heart defects (57.5%), neonatal hyperbilirubinemia (19.7%), and hypothyroidism (39%) were observed, rare conditions such as polydactyly, Ebstein anomaly, epilepsy, epileptic encephalopathy, nephrolithiasis, and cholelithiasis were also reported.</p><p><strong>Conclusion: </strong>The clinical features of Down syndrome observed in Türkiye have been summarized through our cohort. Medical teams need comprehensive knowledge about Down syndrome management. Childhood is recognized as a critical period in Down syndrome care, particularly regarding early diagnosis and treatment of congenital malformations and management of developmental delays.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"17 3","pages":"221-237"},"PeriodicalIF":0.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Siblings with <i>LRPPRC</i> Mutation: Mitochondrial Complex IV Deficiency: Case Report.","authors":"Merve Setenay Akyüzlüer Güneş, Duygu Duman, Emine Kübra Şen, Miraç Yıldırım, Elif Özsu, Ömer Erdeve, Seda Kaynak Şahap, Fatma Tuba Eminoğlu, Engin Köse","doi":"10.1159/000548731","DOIUrl":"10.1159/000548731","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial diseases caused by mutations in the <i>LRPPRC</i> gene are rare and lead to multisystemic dysfunction. We report two siblings from consanguineous Iraqi parents, both harboring a rare homozygous deletion in <i>LRPPRC</i> (c.2726_2728del; p.Lys909del), previously reported in one other patient. These cases contribute to the expanding phenotypic and geographic spectrum of <i>LRPPRC</i>-related mitochondrial disease.</p><p><strong>Case presentation: </strong>The younger sibling, a 9-year-old girl, presented with severe growth retardation, global developmental delay, hypotonia, spastic ataxic gait, and lactic acidosis. Magnetic resonance imaging showed symmetrical hyperintensities in the mesencephalon and thalami, cerebellar atrophy, and an inverted lactate peak on spectroscopy. Hypertrophic cardiomyopathy was also detected. The older sibling, aged 13, exhibited milder manifestations, including axial hypotonia, tremor, ataxia, and persistent hyperlactatemia. Both siblings had elevated lactate levels but otherwise normal metabolic panels. Whole exome sequencing revealed a homozygous mutation in the <i>LRPPRC</i> gene (c.2726_2728del; p.Lys909del) in both patients.</p><p><strong>Conclusions: </strong>These cases highlight the clinical variability of <i>LRPPRC</i>-related disorders. Our report underscores the importance of considering <i>LRPPRC</i> mutations in the differential diagnosis of early-onset neurodevelopmental delay and multisystemic dysfunction with lactic acidosis, especially in populations with high rates of consanguinity. Early genetic diagnosis via whole exome sequencing is essential for accurate diagnosis, genetic counseling, and family planning.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"17 3","pages":"288-295"},"PeriodicalIF":0.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000549839","DOIUrl":"10.1159/000549839","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000540925.].</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"307-308"},"PeriodicalIF":0.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000550895","DOIUrl":"10.1159/000550895","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000547016.].</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"306"},"PeriodicalIF":0.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CRTAP</i>-Related Osteogenesis Imperfecta: Clinical Variability and a Potential Founder Variant in <i>CRTAP</i>.","authors":"André M Travessa, José Carlos Romeu, Teresa Mirco, Carolina Vaz-de-Macedo, Maria João Palma, Silvia Modamio-Høybjør, Céu Barreiros, Andreia Magalhães, Rafael Correia Barão, Karen E Heath, Ana Berta Sousa","doi":"10.1159/000547923","DOIUrl":"10.1159/000547923","url":null,"abstract":"<p><strong>Introduction: </strong><i>CRTAP</i>-related osteogenesis imperfecta (OI) is a form of OI that ranges from moderate (type IV) to extremely severe (type II) and is caused by biallelic variants in the <i>CRTAP</i> gene. To date, only about 30 cases have been reported in the literature.</p><p><strong>Methods: </strong>We describe two adults and one fetus with molecularly confirmed <i>CRTAP</i>-related OI.</p><p><strong>Results: </strong>The phenotype varied extensively in terms of severity and clinical features, ranging from moderate (type IV) to severe (type III) and including cases with prenatal fractures as well as one case with a low number of fractures and no prenatal fractures. Interestingly, 1 patient presented with high myopia and bilateral retinal detachment, which have not been previously reported in OI type VII. Regarding molecular results, we identified three <i>CRTAP</i> variants that have not been previously reported in the literature. One of the variants was found in both a woman and an unrelated fetus of Cape Verdean descent, suggesting that the carrier frequency of this variant in the Cape Verde population may be relatively high.</p><p><strong>Conclusion: </strong>We expand the clinical spectrum of patients with <i>CRTAP</i> variants and highlight the clinical variability of this extremely rare type of OI, which may present with either prenatal or postnatal onset. Our findings also underscore the importance of investigating the role of <i>CRTAP</i> in extra-skeletal tissues and assessing potential founder effects in underrepresented populations.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"213-220"},"PeriodicalIF":0.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Insights into Congenital Generalized Lipodystrophy Type 4: A Case Report.","authors":"Nagehan Bilgeç, Beray Selver Eklioğlu, Halil İbrahim Gün, Özgür Balasar, Mehmet Emre Atabek, Hüseyin Çaksen","doi":"10.1159/000548361","DOIUrl":"10.1159/000548361","url":null,"abstract":"<p><strong>Introduction: </strong>Lipodystrophy syndromes (LS) represent a clinically and genetically heterogeneous group of disorders of adipose tissue. LS are characterized by a partial or generalized deficiency of adipose tissue and variations in fat distribution throughout the body. Metabolic complications serve as significant determinants of morbidity and mortality in these syndromes.</p><p><strong>Case presentation: </strong>The patient was assessed for general lipodystrophy and myopathy findings, and a <i>CAVIN1</i> mutation was identified by next generation sequencing. Our patient exhibited low leptin and vitamin D levels, categorized as metabolic disorders, alongside increased insulin resistance. Additionally, low insulin-like growth factor 1 levels and delayed puberty were noted as hormonal disorders. Osteoporosis, scoliosis, ventricular extrasystoles, and ventricular tachycardia were observed as morbid conditions during the follow-up. We detected hypoplasia of the anterior cerebral artery and the internal carotid artery, which are seen as ultrarare. A coexistent structural cerebral vascular anomaly has not been previously reported in congenital generalized lipodystrophy type 4.</p><p><strong>Conclusion: </strong>Congenital generalized lipodystrophy type 4 should be considered when associated with elevated liver enzyme levels and creatine phosphokinase values. Determining the underlying genetic cause enables an expeditious monitoring and treatment process.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"280-287"},"PeriodicalIF":0.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12600033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different Clinic, Different Diagnosis: Tyrosinemia Type 3.","authors":"Hacer Basan, Serdar Ceylaner, Aynur Küçükcongar Yavaş","doi":"10.1159/000547808","DOIUrl":"10.1159/000547808","url":null,"abstract":"<p><strong>Introduction: </strong>Tyrosinemia type III is an extremely rare autosomal recessive metabolic disorder resulting from biallelic pathogenic mutations in the <i>HPD</i> gene. To date, only a limited number of cases have been reported worldwide, and the full spectrum of clinical manifestations remains incompletely understood. While neurodevelopmental abnormalities are the most commonly described features, ocular involvement has rarely been documented.</p><p><strong>Case presentation: </strong>Here, we present a 9-month-old girl who exhibited strikingly atypical ocular symptoms characterized by persistent severe photophobia and allergic conjunctivitis at initial presentation. This combination of findings has been reported only sporadically in the literature. Biochemical and genetic investigations confirmed the diagnosis by identifying two novel heterozygous variants in the <i>HPD</i> gene. Implementation of a phenylalanine- and tyrosine-restricted diet led to a marked reduction in plasma tyrosine concentrations and improvement in clinical symptoms.</p><p><strong>Conclusion: </strong>This case underscores the diagnostic importance of considering inherited metabolic disorders in infants presenting with severe photosensitivity and conjunctival irritation, even in the absence of other systemic features. Furthermore, it highlights the need for long-term follow-up to monitor potential neurological and ocular complications associated with persistently elevated tyrosine levels.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":" ","pages":"276-279"},"PeriodicalIF":0.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}