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Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane‐bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi‐allelic PIGH variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI‐anchored protein (GPI‐AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant., GPIs are synthetized by the GPI‐GnT, comprising PIGH, on the cytoplasmic membrane of ER from a phosphatidylinositol and a N‐acetylglucosamine. Once flipped to the luminal side of the ER and further synthesized, GPIs are added to proteins to form GPI‐APs. GPI‐APs are transported to the cytoplasmic membrane via the Golgi. Features of individuals with bi‐allelic PIGH variants are presented according to their frequency.

CDC42BPB encodes MRCKβ (myotonic dystrophy-related Cdc42-binding kinase beta), a serine/threonine protein kinase, and a downstream effector of CDC42, which has recently been associated with Takenouchi-Kosaki syndrome, an autosomal dominant neurodevelopmental disorder. We identified 12 heterozygous predicted deleterious variants in CDC42BPB (9 missense, 2 frameshift, and 1 nonsense) in 14 unrelated individuals (confirmed de novo in 11/14) with neurodevelopmental disorders including developmental delay/intellectual disability, autism, hypotonia, and structural brain abnormalities including cerebellar vermis hypoplasia and agenesis/hypoplasia of the corpus callosum. The frameshift and nonsense variants in CDC42BPB are expected to be gene-disrupting and lead to haploinsufficiency via nonsense-mediated decay. All missense variants are located in highly conserved and functionally important protein domains/regions: 3 are found in the protein kinase domain, 2 are in the citron homology domain, and 4 in a 20-amino acid sequence between 2 coiled-coil regions, 2 of which are recurrent. Future studies will help to delineate the natural history and to elucidate the underlying biological mechanisms of the missense variants leading to the neurodevelopmental and behavioral phenotypes.

Background Myositis Ossificans Cicumscripta is a rare condition characterized by aberrant bone formation in paramuscular soft tissue of the extremities usually associated with trauma or a genetic mutation. Very few cases involve the head or neck and it is rarely found in the pediatric population. Objectives We present a case of a 5-month old with a rapidly growing posterior neck mass suspicious for neoplasia, which was treated with surgical resection and found to be a non-traumatic, non-genetic form of Myositis Ossificans. The workup, treatment, and findings of the patient are outlined and a review of the literature on this disease is discussed. Conclusion Myositis Ossificans is characterized by aberrant bone formation typically occurring after trauma but may be secondary to an underlying genetic abnormality. The case presented in the absence of trauma or an underlying genetic abnormality and is therefore an exceedingly rare instance of the sporadic form that presented spontaneously in the head and neck of a pediatric patient.