ソトス症候群

[This corrects the article DOI: 10.3389/fped.2023.1184529.].

Malan syndrome is a rare overgrowth disorder caused by deletions or pathogenic variants in the NFIX gene. Here, we present the case of a Japanese male infant with Malan syndrome, which was caused by a novel frameshift variant resulting from an eight-base insertion in Exon 2 of the NFIX gene. Echocardiography revealed dilatation of the pulmonary artery without hemodynamic abnormalities. Malan syndrome shares many clinical features with Sotos syndrome, including overgrowth, macrocephaly, developmental delay, and intellectual disability. Therefore, molecular genetic testing is required for diagnosis. Pathogenic variants in the NFIX gene have also been reported in individuals with Marshall-Smith syndrome. Some individuals exhibit phenotypic overlap between Malan syndrome and Marshall-Smith syndrome. Our patient was diagnosed with Malan syndrome because he had a frameshift variant in Exon 2, resulting in haploinsufficiency, and exhibited macrocephaly, but not proptosis or micrognathia. To our knowledge, this is the second reported case in the literature of concomitant pulmonary artery dilatation in Malan syndrome.

BACKGROUND: Sotos syndrome is a rare overgrowth-intellectual disability(OGID) disorder typically associated with developmental delay that stabilizes or improves with early intervention. CASE PRESENTATION: We report a 17-month-old boy with classic clinical features of Sotos syndrome who presented with severe speech and motor delay. Whole-exome sequencing(WES) revealed a novel de novo nonsense pathogenic variant in NSD1:c.3910 C > T (p.Gln1304Ter), which is predicted to truncate multiple functional domains, including the SET(Su(var)3-9, Enhancer-of-zeste, and Trithorax) catalytic domain. Despite early and continuous rehabilitation, his developmental quotient(DQ) decreased from 45.8 at 17 months to 39.9 at 28 months, indicating slow and limited developmental progress over time. Brain MRI (magnetic resonance imaging) revealed corpus callosum abnormalities and reduced white matter volume. CONCLUSIONS: This is the first report of Sotos syndrome caused by the NSD1:c.3910 C > T (p.Gln1304Ter) pathogenic variant. Beyond expanding the spectrum of pathogenic variants, this case highlights a relatively severe neurodevelopmental profile with persistently limited progress, underscoring the importance of early genetic diagnosis, sustained multidisciplinary rehabilitation, and long-term follow-up to optimize outcomes in affected children.

Sotos syndrome (SS) is a rare genetic disorder characterized by overgrowth, distinctive facial features, and dentofacial abnormalities. While its oral manifestations are well documented in childhood, there is limited evidence regarding dental management in adults. This case report, prepared in accordance with the CARE guidelines, describes a 28-year-old woman diagnosed with SS who presented with typical craniofacial features of the condition. The patient sought care for partial edentulism, and oral rehabilitation with removable partial dentures was planned. The treatment approach considered the anatomical, functional, and cognitive limitations associated with the syndrome, and included a preventive phase, progressive prosthetic adaptation, and periodic clinical follow-ups. After four months, the patient showed satisfactory prosthetic adaptation, functional stability, and good oral hygiene. A scoping review of the literature was conducted following PRISMA-ScR guidelines. Searches were performed in the PubMed and Web of Science databases to identify studies reporting dental treatments in patients with a confirmed diagnosis of SS. Six case reports published between 2006 and 2023 were included. The most frequently reported oral manifestations were severe malocclusions, hypodontia, supernumerary teeth, and skeletal abnormalities. Management was interdisciplinary, with a focus on orthodontic therapies in younger patients and implant-supported rehabilitations in adults. Removable prosthetic rehabilitation represents a valid and effective alternative for adults with SS, particularly when implant-based treatments are contraindicated. This case contributes new clinical evidence and highlights the importance of personalized approaches and continuous follow-up in this patient population.

BACKGROUND: Leukemia is the most common malignancy in children, while type 1 diabetes mellitus (T1DM) is one of the most prevalent autoimmune diseases among children. The etiology of both conditions is still largely unexplained, yet emerging evidence suggests certain similarities in environmental exposures and genetic predispositions. In this case-series, we sought a new potential factor behind the co-occurrence of leukemia and T1DM by thoroughly reviewing the medical records of patients diagnosed with both diseases. METHODS: We conducted a retrospective case series at Tampere University Hospital, Finland, by identifying pediatric patients diagnosed with both acute leukemia and T1DM from 1990 to 2023 using (International Classification of Diseases-10th revision) ICD-10 codes. Clinical and laboratory data, including leukemia subtype, age at diagnosis, treatments, comorbidities, and medical history, were collected, reviewed and analyzed descriptively. Study protocol was locally approved, and patient health data privacy was respected. RESULTS: Among 12 initially identified cases, seven met the inclusion criteria. Five cases were diagnosed with B-cell acute lymphoblastic leukemia (B-ALL), one with T-cell ALL (T-ALL), and one with acute myeloid leukemia. The mean age at leukemia diagnosis was 8.7 years (range from 0.7 to 15.3), while the mean age at T1DM diagnosis was 11.8 years (range from 7.5 to 17.8). In five cases, leukemia preceded T1DM, with two cases linked to asparaginase-induced pancreatitis. In two cases, T1DM developed before leukemia. Additional comorbidities included Down syndrome, Sotos syndrome, celiac disease, epilepsy, and Sweet's syndrome. CONCLUSION: This case-series presents findings, which align with previous observations (e.g., Down syndrome, pancreatitis), though a less often reported finding, Sotos syndrome, was also observed.