A Novel RNF216 Variant Causing Gordon Holmes Syndrome in Three Lithuanian Siblings

Phenotypic and Molecular Features of a Large ODDD Family: Expanding the Spectrum of CX43-Related Disorder

We present a family of five siblings who came to our attention with a clinical and radiological diagnosis of familial hypomyelinating leukodystrophy. Despite brain white matter abnormalities being present in all siblings, the clinical phenotype was variable: the three brothers presented with a clear-cut late-onset spastic paraplegia, whereas the two sisters displayed only mild pyramidal signs. Molecular analysis revealed a single relevant variant shared by all affected siblings, namely the likely pathogenic variant c.659C>T (p.Ser220Phe) in the GJA1 gene. Variants in this gene are generally associated with oculodentodigital dysplasia (ODDD), an autosomal dominant condition characterized by distinctive facial features and anomalies of the eyes, teeth, and digits. Neurological features are reported in about 30% of cases. In this family, ODDD manifested as a predominantly neurological phenotype. Although a clear explanation for this uncommon presentation is lacking, shared genetic modifiers, the effect of the specific variant, and a possible patient-population bias may have contributed. This case highlights the wide phenotypic spectrum of CX43-related disorders and suggests the importance of testing the GJA1 gene in individuals with atypical presentations, including predominant or isolated neurological phenotypes such as late-onset spastic paraplegia. MRI findings may also provide a useful diagnostic clue when ODDD is suspected.

Molecular and clinical heterogeneity in an Iranian case series of Joubert syndrome

This study expands the mutational landscape of JS in the Iranian population and underscores the utility of WES as a first-tier diagnostic tool for JS and related ciliopathies.

Intrafamilial Variability in 2 Siblings With TANGO2-Related Disorder.

Two sisters homozygous for the recurrent TANGO2 variant c.460G>A, identified in a family of Hispanic/Latino ancestry, who exhibited divergent clinical presentations highlight intrafamilial variability within the recognized TDD spectrum and underscore the importance of early recognition of neurologic and endocrine features as potential red flags.

Case Report: A novel HNRNPK gene variant causing Au-Kline syndrome; the genotype and phenotype of the oldest individual ever described

This case underscores that the genetic and neuropsychological identification of a neurodevelopmental disorder, together with the integration of tailored psychomotor interventions and contextual adaptations, can improve psychiatric management and daily functioning, and mitigate behavioral decline in adulthood, even following a prolonged diagnostic delay.

King-Denborough syndrome: a clinicogenetic case report

King–Denborough syndrome is a rare RYR1-related congenital myopathy characterized by dysmorphic features, muscle weakness, and susceptibility to malignant hyperthermia, often posing a diagnostic challenge in early infancy. We report a one-year-old female child presenting with developmental delay and generalized hypotonia. Clinical evaluation revealed craniofacial dysmorphism, bilateral ptosis, and esotropia, raising suspicion of an underlying congenital myopathy. Initial laboratory and imaging workup were inconclusive except for transient elevation of creatine kinase. Whole exome sequencing identified a heterozygous missense variant in the RYR1 gene (c.14126C>T; p.Thr4709Met), along with a likely pathogenic FOXP1 variant. In view of the characteristic clinical phenotype, a diagnosis of King–Denborough syndrome was considered. The child was managed with supportive therapy and developmental interventions, and caregivers were counselled regarding the risk of malignant hyperthermia. This case underscores the importance of clinicogenetic correlation in diagnosing rare myopathies and highlights the need for early recognition to enable appropriate counselling and prevention of anaesthetic complications.

“Severe intellectual disability with cardiac and dermatologic involvement due to homozygous METTL23 frameshift mutation: a case report of two Turkish sisters”