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Journal of Medical Genetics Sep 1990
Topics: Abnormalities, Multiple; Adolescent; Birth Weight; Bone and Bones; Child; Child, Preschool; Chromosome Aberrations; Diagnosis, Differential; Facial Bones; Humans; Infant; Skull; Syndrome
PubMed: 2231650
DOI: 10.1136/jmg.27.9.571 -
Epilepsia Open Jun 2021We aimed to describe the phenotypic spectrum of seizures in Sotos syndrome, a genetic condition involving overgrowth, macrocephaly, dysmorphic features, and learning...
We aimed to describe the phenotypic spectrum of seizures in Sotos syndrome, a genetic condition involving overgrowth, macrocephaly, dysmorphic features, and learning disability, in which 60%-90% have NSD1 pathogenic variants. Patients were recruited from clinics and referral from support groups. Those with seizures and a clinical diagnosis of Sotos syndrome were included. Phenotyping data were collected via structured clinical interview and chart review. Forty-nine patients were included. Twenty had NSD1 testing results available; of these, 15 (75%) had NSD1 pathogenic variants. Seizure onset age ranged from 3 months to 12 years. Staring spells (absence or focal impaired awareness seizure) were the most frequently reported semiology (33/49; 67%), followed by febrile seizures (25/49; 51%) and afebrile bilateral tonic-clonic seizures (25/49; 51%). Most patients (33/49; 67%) had multiple seizure types. The majority (33/49; 67%) had seizures controlled on a single antiseizure medication or no medication. Nine (18%) had drug-resistant epilepsy. Epilepsy syndromes included febrile seizures plus, Lennox-Gastaut syndrome, childhood absence epilepsy, and generalized tonic-clonic seizures alone. The seizure phenotype in Sotos syndrome most commonly involves staring spells, afebrile tonic-clonic seizures or febrile convulsions; however, other seizure types may occur. Seizures are typically well-controlled with medication, but drug-resistant epilepsy occurs in a minority.
Topics: Child; Epilepsies, Partial; Epilepsy, Absence; Humans; Seizures; Seizures, Febrile; Sotos Syndrome
PubMed: 34033256
DOI: 10.1002/epi4.12484 -
Cancers Oct 2022Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone... (Review)
Review
Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or promoter functions according to the tissue context and we discuss the role of NSD1 in melanoma. Finally, we examine the ongoing efforts to target NSD1 signaling in cancers.
PubMed: 36230787
DOI: 10.3390/cancers14194865 -
Frontiers in Pediatrics 2023Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly,...
INTRODUCTION
Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly, typical facial appearance and different degrees of intellectual disability. Three different types are described caused by variants or deletions/duplications in and genes. We aimed to describe a cohort of pediatric patients reporting the typical and unexpected findings in order to expand the phenotype of this syndrome and trying to find genotype-phenotype correlations.
METHODS
In our referral center, we collected and analyzed clinical and genetic data of 31-patients cohort diagnosed with SS.
RESULTS
All of them presented with overgrowth, typical dysmorphic features and different degree of developmental delay. Although structural cardiac defects have been reported in SS, non-structural diseases such as pericarditis were outstanding in our cohort. Moreover, we described here novel oncological malignancies not previously linked to SS such as splenic hamartoma, retinal melanocytoma and acute lymphocytic leukemia. Finally, five patients suffered from recurrent onychocryptosis that required surgical procedures, as an unreported prevalent medical condition.
DISCUSSION
This is the first study focusing on multiple atypical symptoms in SS at the time that revisits the spectrum of clinical and molecular basis of this heterogeneous entity trying to unravel a genotype-phenotype correlation.
PubMed: 37384309
DOI: 10.3389/fped.2023.1184529 -
Science Advances Jan 2021Proper formation of area identities of the cerebral cortex is crucial for cognitive functions and social behaviors of the brain. It remains largely unknown whether...
Proper formation of area identities of the cerebral cortex is crucial for cognitive functions and social behaviors of the brain. It remains largely unknown whether epigenetic mechanisms, including histone methylation, regulate cortical arealization. Here, we removed SETD2, the methyltransferase for histone 3 lysine-36 trimethylation (H3K36me3), in the developing dorsal forebrain in mice and showed that is required for proper cortical arealization and the formation of cortico-thalamo-cortical circuits. Moreover, conditional knockout mice exhibit defects in social interaction, motor learning, and spatial memory, reminiscent of patients with the Sotos-like syndrome bearing mutations. SETD2 maintains the expression of clustered protocadherin () genes in an H3K36me3 methyltransferase-dependent manner. Aberrant cortical arealization was recapitulated in heterozygous mice. Together, our study emphasizes epigenetic mechanisms underlying cortical arealization and pathogenesis of the Sotos-like syndrome.
PubMed: 33523829
DOI: 10.1126/sciadv.aba1180 -
Journal of Clinical Research in... Aug 2023One-month old breastfeeding infant, full-term birth, with normal anthropometric measurements at birth is referred to Pediatric Nephrology due to a nephrocalcinosis. The...
One-month old breastfeeding infant, full-term birth, with normal anthropometric measurements at birth is referred to Pediatric Nephrology due to a nephrocalcinosis. The patient presents dysmorphic features and heart disease. A metabolic study is conducted on blood and urine yielding results within normal parameters, except for renal concentration test and acidification test. At 6 months of age, patient presents overgrowth, which along with other clinical signs arouse suspicion of Sotos Syndrome. Molecular genetic testing detects heterozygous deletion in 5q35 between bands q35.2 and q35.3, affecting genes NSD1, SLC34A1 and FGFR4, which is compatible with this syndrome and with nephrocalcinosis as a rare association.
PubMed: 37559368
DOI: 10.4274/jcrpe.galenos.2023.2023-3-11 -
Genes Nov 2022Inactivating mutations causing Sotos syndrome have been previously associated with a specific genome-wide DNA methylation (DNAm) pattern. Sotos syndrome is...
BACKGROUND
Inactivating mutations causing Sotos syndrome have been previously associated with a specific genome-wide DNA methylation (DNAm) pattern. Sotos syndrome is characterized by phenotypic overlap with other overgrowth syndromes, and a definite diagnosis might not be easily reached due to the high prevalence of variants of unknown significance (VoUS) that are identified in patients with a suggestive phenotype.
OBJECTIVE
we performed microarray DNAm profiling in a set of 11 individuals with a clinical suspicion of Sotos syndrome and carrying an VoUS or previously unreported variants to solve uncertainty in defining pathogenicity of the observed variants. The impact of the training cohort size on sensitivity and prediction confidence of the classifier was assessed.
RESULTS
The Sotos syndrome-specific DNAm signature was validated in six individuals with a clinical diagnosis of Sotos syndrome and carrying pathogenic variants. Applying this approach to the remaining 11 individuals with variants, we succeeded in confirming pathogenicity in eight subjects and excluding the diagnosis of Sotos syndrome in three. The sensitivity and prediction confidence of the classifier based on the different sizes of the training sets did not show substantial differences, though the overall performance was improved by using a data balancing strategy.
CONCLUSIONS
The present approach solved uncertainty in cases with VoUS, further demonstrating the clinical utility of DNAm profiling.
Topics: Humans; Sotos Syndrome; DNA Methylation; Histone-Lysine N-Methyltransferase; Uncertainty; Growth Disorders
PubMed: 36421837
DOI: 10.3390/genes13112163 -
Frontiers in Neurology 2024Sotos syndrome (SoS) is a rare overgrowth genetic disease caused by intragenic mutations or microdeletions of the gene located on chromosome 5q35. SoS population might...
BACKGROUND
Sotos syndrome (SoS) is a rare overgrowth genetic disease caused by intragenic mutations or microdeletions of the gene located on chromosome 5q35. SoS population might present cognitive impairment and a spectrum of behavioral characteristics, with a worse profile in patients with microdeletion. Although patients with SoS are known to have impaired sleep habits, very little data are available. The present study aimed to assess the prevalence of sleep disorders (SDs) in a pediatric cohort of patients with SoS and their correlation with neuropsychiatric profiles.
METHODS
We included patients with a SoS diagnosis and age < 18 years; all patients underwent a comprehensive neuropsychological assessment, including evaluation of cognition, adaptive functions through the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and behavioral problems using the Achenbach Child Behavior Checklist (CBCL) and Conners' Parent Rating Scale-Revised (CPRS-R:L) questionnaire. To investigate the presence of SD parents, the Sleep Disturbance Scale for Children (SDSC) was completed.
RESULTS
Thirty-eight patients (M 61%, F 39%, mean age 11.1 ± 4.65 years) were included in the study. Although only two had a prior SD diagnosis, 71.1% (N = 27) exhibited pathological scores on SDSC. No statistically significant associations were found between positive SDSC results and genetic microdeletion, intellectual disability (ID), or other medical conditions/treatments. However, a positive correlation emerged between SDSC scores and Conners' Global Index ( = 0.048) and Restless/Impulsive ( = 0.01) scores, CBCL externalizing ( = 0.02), internalizing (p = 0.01), and total scores ( = 0.05). Conversely, a negative linear relationship was observed between the SDSC score and the ABAS GAC and ABAS CAD scores ( = 0.025).
CONCLUSION
We detected an SD in 71.1% of our sample, with a positive relation between SD and internalizing and externalizing symptom levels, especially hyperactivity and impulsivity. Our study demonstrated a high prevalence of SD in pediatric patients with SoS, highlighting that all patients should be screened for this problem, which has a great impact on the quality of life of patients and their families.
PubMed: 38434199
DOI: 10.3389/fneur.2024.1360055 -
Annals of Pediatric Endocrinology &... Sep 2013Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation... (Review)
Review
Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future.
PubMed: 24904861
DOI: 10.6065/apem.2013.18.3.101 -
Medicine Dec 2023Sotos syndrome is an congenital overgrowth syndrome characterized by the primary features including overgrowth, distinctive facial features, learning disability, and...
RATIONALE
Sotos syndrome is an congenital overgrowth syndrome characterized by the primary features including overgrowth, distinctive facial features, learning disability, and accompanied with various second features. NSD1 deletion or mutation is a major pathogenic cause. Although there are some reports on treatment of this disease worldwide, less cases under treatment have been published in China.
PATIENT CONCERNS
A 1-year-old boy had macrocephaly, gigantism, excessive high body height, a particular face and delayed development, with a pathogenic gene of NSD1 (NM_022455.5:c.3536delA in exon 5).
DIAGNOSIS AND INTERVENTIONS
The child was definitely diagnosed as Sotos syndrome and have 3 months' combination treatment of traditional Chinese medicine and rehabilitation.
OUTCOMES
The child made a great progress in global development.
LESSONS
This case firstly describes the traditional Chinese medicine and rehabilitation to treat Sotos syndrome in China. There is no radical cure, but our therapy could improve the prognosis and the life quality of the patient. Therefore, this case provides a reference to the clinical treatment of Sotos syndrome.
Topics: Child; Male; Humans; Infant; Sotos Syndrome; Histone Methyltransferases; Histone-Lysine N-Methyltransferase; Medicine, Chinese Traditional; Mutation
PubMed: 38050304
DOI: 10.1097/MD.0000000000036169