Intellectual disability with speech delay and behavioural abnormalities, as well as hypotonia, seizures, feeding difficulties and craniofacial dysmorphism, are the main symptoms associated with pathogenic variants of the ZMYND11 gene. The range of clinical manifestations of the ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present two previously unreported paediatric patients with neurodevelopmental challenges, who were diagnosed with missense variants in the ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinaemic hypoglycaemia (HH), a symptom that was not described before in published works. The reason for the occurrence of HH in our proband is not clear, so we try to explain the origin of this symptom in the context of the ZMYND11 syndrome. Thus, this paper contributes to knowledge on the range of possible manifestations of the ZMYND disease and provides further evidence supporting its association with neurodevelopmental challenges.

Intellectual disability with speech delay and behavioural abnormalities as well as hypotonia, seizures, feeding difficulties and cra-niofacial dysmorphism are the main symptoms associated with pathogenic variants of ZMYND11 gene. The range of clinical mani-festations of ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present 2 previ-ously unreported paediatric patients with neurodevelopmental features diagnosed with missense variants in ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinemic hypoglycaemia (HH), a symptom that was not de-scribed before in published works. Although the reason for the occurrence of HH in our proband is not clear, it is likely that it broadens the spectrum of symptoms characteristic of ZMYND11 syndrome. Thus, this paper contributes to extending the range of possible manifestations of ZMYND disease and further supports its association with neurodevelopmental challenges.

Background: Börjeson–Forssman–Lehmann syndrome (BFLS; OMIM 301900; ORPHA 127) is a rare X-linked neurodevelopmental disorder caused by pathogenic variants in the PHF6 gene. The aim of this case series was to describe the clinical and endocrine phenotype of two genetically confirmed patients with BFLS and to highlight phenotypic variability relevant to diagnosis and long-term clinical management. Methods: We conducted a case series of two patients with genetically confirmed BFLS who were managed at a pediatric endocrinology center. Clinical data were collected from medical records, including perinatal and developmental history, growth parameters, endocrine assessments, systemic manifestations, genetic findings, treatment, and follow-up. Genetic diagnosis was established using next-generation sequencing-based whole-exome sequencing. Results: Both patients presented with global developmental delay, intellectual disability, short stature, and characteristic dysmorphic features. Endocrine abnormalities included hypothyroidism and growth impairment in both patients. Patient 1 additionally presented with central obesity, delayed skeletal maturation, hypogonadotropic hypogonadism, delayed puberty, and vitamin D insufficiency requiring treatment. Whole-exome sequencing identified pathogenic PHF6 variants in both patients. Patient 1 also had a history of Wilms tumor, representing a previously unreported finding in association with BFLS. Conclusions: These cases illustrate the substantial phenotypic variability of BFLS and emphasize the importance of regular endocrine surveillance, particularly assessment of growth, thyroid function, and pubertal development. The coexistence of BFLS and Wilms tumor represents a novel observation; however, a causal relationship cannot be established from a single case and requires further investigation.