SRRM2-related neurodevelopmental disorder is a recently described genetic diagnosis caused by loss-of-function variants in SRRM2. In order to understand the clinical spectrum of SRRM2-related neurodevelopmental disorder, we performed a retrospective exome data and clinical chart review at a single tertiary children's hospital,Children's Hospital of Philadelphia (CHOP). Among approximately 3100 clinical exome sequencing cases performed at CHOP, we identified three patients with SRRM2 loss-of-function pathogenic variants, in addition to one patient previously described in the literature. Common clinical features include developmental delay, attention deficit hyperactivity disorder, macrocephaly, hypotonia, gastroesophageal reflux, overweight/obesity, and autism. While developmental disabilities are commonly seen in all individuals with SRRM2 variants, the degree of developmental delay and intellectual disability is variable. Our data suggest that SRRM2-related neurodevelopmental disorder can be identified in 0.3% of individuals with developmental disabilities receiving exome sequencing.

Kabuki syndrome is a recognizable Mendelian disorder characterized by the clinical constellation of childhood hypotonia, developmental delay or intellectual impairment, and characteristic dysmorphism resulting from monoallelic pathogenic variants in KMT2D or KDM6A. In the medical literature, most reported patients are children, and data is lacking on the natural history of the condition across the lifespan, with little known about adult‐specific presentations and symptoms. Here, we report the results of a retrospective chart review of eight adult patients with Kabuki syndrome, seven of whom are molecularly confirmed. We use their trajectories to highlight the diagnostic challenges unique to an adult population, expand on neurodevelopmental/psychiatric phenotypes across the lifespan, and describe adult‐onset medical complications, including a potential cancer risk and unusual and striking premature/accelerated aging phenotype.

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Eukaryotic translation elongation factor 2 (eEF2), encoded by the gene EEF2, is an essential factor involved in the elongation phase of protein translation. A specific heterozygous missense variant (p.P596H) in EEF2 was originally identified in association with autosomal dominant adult‐onset spinocerebellar ataxia‐26 (SCA26). More recently, additional heterozygous missense variants in this gene have been described to cause a novel, childhood‐onset neurodevelopmental disorder with benign external hydrocephalus. Herein, we report two unrelated individuals with a similar gene‐disease correlation to support this latter observation. Patient 1 is a 7‐year‐old male with a previously reported, de novo missense variant (p.V28M) who has motor and speech delay, autism spectrum disorder, failure to thrive with relative macrocephaly, unilateral microphthalmia with coloboma and eczema. Patient 2 is a 4‐year‐old female with a novel de novo nonsense variant (p.Q145X) with motor and speech delay, hypotonia, macrocephaly with benign ventricular enlargement, and keratosis pilaris. These additional cases help to further expand the genotypic and phenotypic spectrum of this newly described EEF2‐related neurodevelopmental syndrome.