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Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the SHANK3 gene. SHANK3 codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (

Tenorio syndrome (TNORS) (OMIM #616260) is a relatively recent disorder with very few cases described so far. Clinical features included macrocephaly, intellectual disability, hypotonia, enlarged ventricles and autoimmune diseases. Molecular underlying mechanism demonstrated missense variants and a large deletion encompassing RNF125, a gene that encodes for an U3 ubiquitin ligase protein. Since the initial description of the disorder in six patients from four families, several new patients were diagnosed, adding more evidence to the clinical spectrum. In this article, we described 14 additional cases with deep phenotyping and make an overall review of all the cases with pathogenic variants in RNF125. Not all patients presented with overgrowth, but instead, most patients showed a common pattern of neurodevelopmental disease, macrocephaly and/or large forehead. Segregation analysis showed that, though the variant was inherited in some patients from an apparently asymptomatic parent, deep phenotyping suggested a mild form of the disease in some of them. The mechanism underlying the development of this disease is not well understood yet and the report of further cases will help to a better understanding and clinical characterization of the syndrome. [ABSTRACT FROM AUTHOR]

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 NSD1, NFIX and APC2 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lourdes, Mario, Didac, Mercè, Loreto, Leticia, Lucia, Martínez-Monseny and Mercedes.)