Gastrointestinal (GI) problems are common in Phelan-McDermid syndrome (PMS). Chewing and swallowing difficulties, dental problems, reflux disease, cyclic vomiting, constipation, incontinence, diarrhoea, and nutritional deficiencies have been most frequently reported. Therefore, this review summarises current findings on GI problems and addresses the fundamental questions, which were based on parental surveys, of how frequent GI problems occur in PMS, what GI problems occur, what consequences (e.g., nutritional deficiencies) GI problems cause for individuals with PMS, and how GI problems can be treated in individuals with PMS. Our findings show that gastrointestinal problems have a detrimental effect on the health of people with PMS and are a significant burden for their families. Therefore, we advise evaluation for these problems and formulate care recommendations.

Background: Sotos syndrome is a genetic disorder caused by NSD1 gene (nuclear receptor binding SET domain containing protein 1) variants and characterized by overgrowth, macrocephaly, learning disabilities, and co-occurring neuropsychiatric symptoms. Methods: Literature sources published in 2002–2023 were selected and analyzed from PubMed and Google Scholar databases. Results: Neuropsychiatric symptoms are observed among children and adolescents with Sotos syndrome. The majority have intellectual disabilities or borderline intellect. Verbal IQ is higher than performance IQ. Individuals display difficulties in expressing language. Aggression is reported by parents. Children express autistic behavior, ADHD, anxiety based on phobias, and early bedtime-wake times. Conclusions: Sotos syndrome is associated with neuropsychiatric disorders in children. Slow intellectual and language development, aggressive outbursts, anxiety, autism spectrum disorder, and hyperactivity are present in the newest studies. Comprehensive assistance is needed for Sotos syndrome patients in responding to areas of difficulty. There is still a lack of research on the developmental characteristics of these children and the possibilities of improving psychosocial adaptation by providing multidisciplinary long-term medical, educational, and social care.

Most genetic variants are rare and specific to the population, highlighting the importance of characterizing local population genetic diversity. Many countries have initiated population-based whole-genome sequencing (WGS) studies. Genomic variation within Lithuanian families are not available in the public databases. Here, we describe initial findings of a high-coverage (an average of 36.27×) whole genome sequencing for 25 trios of the Lithuanian population. Each genome on average carried approximately 4,701,473 (±28,255) variants, where 80.6% (3,787,626) were single nucleotide polymorphisms (SNPs), and the rest 19.4% were indels. An average of 12.45% was novel according to dbSNP (build 150). The WGS structural variation (SV) analysis identified on average 9133 (±85.10) SVs, of which 95.85% were novel. De novo single nucleotide variation (SNV) analysis identified 4417 variants, where 1.1% de novo SNVs were exonic, 43.9% intronic, 51.9% intergenic, and the rest 3.13% in UTR or downstream sequence. Three potential pathogenic de novo variants in the ZSWIM8, CDC42EP1, and RELA genes were identified. Our findings provide useful information on local human population genomic variation, especially for de novo variants, and will be a valuable resource for further genetic studies, and medical implications.

Osteogenesis imperfecta (OI), also known as brittle bone disease, belongs to a rare heterogeneous group of inherited connective tissue disorders. In experienced prenatal centers, severe cases of OI can be suspected before birth from the first trimester prenatal ultrasound screening. In this article, we describe a case report of OI suspected at the 26th week of gestation and the patient’s outcomes in infancy one year after birth, as well as compare our case to other prenatally or soon-after-birth suspected and/or diagnosed OI clinical case reports in the literature. This case was managed by a multidisciplinary team. In this clinical case, OI was first suspected when prenatal ultrasound revealed asymmetric intrauterine growth restriction and skeletal dysplasia features. The diagnosis was confirmed after birth using COL1A1 gene variant detection via exome sequencing; the COL1A1 gene variant causes OI types I–IV. The familial history was negative for both pregnancy-related risk factors and genetic diseases. At one year old, the patient’s condition remains severe with bisphosphonate therapy.

Some people resist or recover from health challenges better than others. We studied Lithuanian clean-up workers of the Chornobyl nuclear disaster (LCWC) who worked in the harshest conditions and, despite high ionising radiation doses as well as other factors, continue ageing relatively healthily. Thus, we hypothesised that there might be individual features encoded by the genome which act protectively for better adaptiveness and health that depend on unique positive selection signatures. Whole-genome sequencing was performed for 40 LCWC and a control group composed of 25 men from the general Lithuanian population (LTU). Selective sweep analysis was performed to identify genomic regions which may be under recent positive selection and determine better adaptiveness. Twenty-two autosomal loci with the highest positive selection signature values were identified. Most important, unique loci under positive selection have been identified in the genomes of the LCWC, which may influence the survival and adaptive qualities to extreme conditions, and the disaster itself. Characterising these loci provide a better understanding of the interaction between ongoing microevolutionary processes, multifactorial traits, and diseases. Studying unique groups of disease-resistant individuals could help create new insights for better, more individualised, disease diagnostics and prevention strategies.

Background/Objectives: Overgrowth syndromes (OGSs) are a heterogeneous group of rare conditions marked by excessive growth and variable neurodevelopmental and systemic features. They are broadly classified into generalized overgrowth (GOG) and segmental overgrowth (SOG), which differ in clinical presentation and genetic mechanisms. However, many cases remain genetically unresolved, especially in underrepresented populations. Methods: We analyzed a binational cohort of patients from Poland and Lithuania with suspected OGSs, using detailed clinical evaluation and exome sequencing (ES) from blood-derived DNA. Variants were interpreted using current clinical guidelines, and phenotypes were compared between the GOG and SOG groups. Results: Patients with GOG more often showed developmental delay, intellectual disability, neurological issues, and joint laxity, while vascular malformations were more common in patients with SOG. Dysmorphic features appeared earlier in the SOG group, but became more pronounced over time in the GOG group. Genetic analysis led to the identification of definitive diagnoses in 25% of individuals. Pathogenic variants were identified in the genes involved in chromatin regulation and epigenetic control (DNMT3A, EED, KMT5B, CHD3, and NSD1), along with novel variants expanding the known spectrum. Conclusions: These findings provide valuable insights into the genetic architecture of OGSs in underrepresented Central and North-Eastern European populations, supporting the development of region-specific diagnostic and surveillance strategies.