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KMT2E‐related neurodevelopmental disorder is a recently described intellectual disability syndrome often with speech difficulties. Here, we describe an individual with a heterozygous frameshift variant in KMT2E (NM_182931.2:c.2334_2337delTTAC, p.[Tyr779AlafsTer41]), intellectual disability, cerebellar hypoplasia, and velopharyngeal dysfunction. This case suggests potential mechanisms of speech disturbance in the disorder, requiring further investigation. [ABSTRACT FROM AUTHOR]

Legius syndrome is a disorder of the RAS and mitogen‐activated protein kinase (MAPK) pathway first described in 2007 by Eric Legius, et al., that has been considered a milder phenotype than reported in the RASopathy neurofibromatosis type 1 (NF1). However, with approximately 200 cases reported in the literature, the Legius syndrome phenotype remains to be fully characterized. We report a child who presented with moyamoya syndrome and who has Legius syndrome due to a pathogenic variant in SPRED1. Vascular complications such as moyamoya syndrome have been reported in NF1. However, this association has not been reported in Legius syndrome. This child's case may represent an expansion of the clinical phenotype of Legius syndrome, and further study is needed. We emphasize the importance of obtaining neuroimaging studies in patients with Legius syndrome who present with new neurologic deficits. [ABSTRACT FROM AUTHOR]

Homozygosity for nonsense variants in CEP55 has been associated with a lethal condition characterized by multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH syndrome) also known as Meckel‐like syndrome. Missense variants in CEP55 have not previously been reported in association with disease. Here we describe seven living individuals from five families with biallelic CEP55 variants. Four unrelated individuals with microcephaly, speech delays, and bilateral toe syndactyly all have a common CEP55 variant c.70G>A p.(Glu24Lys) in trans with nonsense variants. Three siblings are homozygous for a consensus splice site variant near the end of the gene. These affected girls all have severely delayed development, microcephaly, and varying degrees of lissencephaly/pachygyria. Here we compare our seven patients with three previously reported families with a prenatal lethal phenotype (MARCH syndrome/Meckel‐like syndrome) due to homozygous CEP55 nonsense variants. Our series suggests that individuals with compound heterozygosity for nonsense and missense variants in CEP55 have a different viable phenotype. We show that homozygosity for a splice variant near the end of the CEP55 gene is also compatible with life. [ABSTRACT FROM AUTHOR]

Background Mucopolysaccharidosis type III is a progressive disease with worsening airway, pulmonary, and cardiac involvement that may complicate anesthetic care. Aim To prospectively evaluate the incidence of airway issues and complications during magnetic resonance imaging (MRI) and lumbar puncture (LP) during general anesthesia with a native airway for patients with mucopolysaccharidosis type III. Method The study was a part of the natural history study. Anesthesia was induced with sevoflurane, which was discontinued after intravenous access was obtained. General anesthesia with a native airway was provided by dexmedetomidine and propofol. Dexmedetomidine (0.5 μg·kg−1) was administered over 5 min followed by a continuous infusion at 0.5 μg·kg−1·h−1. A continuous infusion of propofol was started at 150 μg·kg−1·min−1. A bolus dose of propofol (1 mg·kg−1) was administered and the propofol infusion was increased as needed. Airway management and vital signs were recorded for the entire procedure until discharge. Results Twenty-five patients (6.9 ± 3.1 years) received total of 43 MRI and LP procedures in the cohort. No patient failed sedation. Although mask induction with sevoflurane was not clinically problematic, upper airway obstruction was noted during 14 procedures (33%). This required the application of continuous positive airway pressure, temporary oral airway placement, jaw thrust, or shoulder roll. Airway dynamics improved once the anesthesia was transitioned to intravenous anesthetic agents. Although a small shoulder roll was needed to improve airway patency for 11 cases (26%), a large shoulder roll tended to make the upper airway obstruction worse. Oxygen desaturation (≤90%) was noted during MRI in three cases (7%). Conclusion A combination of dexmedetomidine and propofol provided effective general anesthesia with a native airway during the procedures. Although upper airway obstruction was noted, it resolved with simple airway maneuvers without further airway intervention. [ABSTRACT FROM AUTHOR]