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Supplemental Material, sj-pdf-3-jcn-10.1177_08830738211001209 for Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic by Michelle Kowanda, Lindsey Cartner, Catherine Kentros, Alexa R. Geltzeiler, Kaitlyn E. Singer, W. Curtis Weaver, Christopher D. Lehman, Simone Smith, Rebecca Sheedy Smith, Lauren Kasparson Walsh, Katharine Diehl, Natalie Nagpal, Elizabeth Brooks, Caroline M. Mebane, Ashley L. Wilson, Alison R. Marvin, L. Casey White, J. Kiely Law, William Jensen, Amy M. Daniels, Jennifer Tjernagel, LeeAnne Green Snyder, Cora M. Taylor and Wendy K. Chung in Journal of Child Neurology

Supplemental Material, sj-pdf-1-jcn-10.1177_08830738211001209 for Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic by Michelle Kowanda, Lindsey Cartner, Catherine Kentros, Alexa R. Geltzeiler, Kaitlyn E. Singer, W. Curtis Weaver, Christopher D. Lehman, Simone Smith, Rebecca Sheedy Smith, Lauren Kasparson Walsh, Katharine Diehl, Natalie Nagpal, Elizabeth Brooks, Caroline M. Mebane, Ashley L. Wilson, Alison R. Marvin, L. Casey White, J. Kiely Law, William Jensen, Amy M. Daniels, Jennifer Tjernagel, LeeAnne Green Snyder, Cora M. Taylor and Wendy K. Chung in Journal of Child Neurology

Supplemental Material, sj-pdf-2-jcn-10.1177_08830738211001209 for Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic by Michelle Kowanda, Lindsey Cartner, Catherine Kentros, Alexa R. Geltzeiler, Kaitlyn E. Singer, W. Curtis Weaver, Christopher D. Lehman, Simone Smith, Rebecca Sheedy Smith, Lauren Kasparson Walsh, Katharine Diehl, Natalie Nagpal, Elizabeth Brooks, Caroline M. Mebane, Ashley L. Wilson, Alison R. Marvin, L. Casey White, J. Kiely Law, William Jensen, Amy M. Daniels, Jennifer Tjernagel, LeeAnne Green Snyder, Cora M. Taylor and Wendy K. Chung in Journal of Child Neurology

International audience; Frontonasal dysplasias are rare congenital malformations of frontonasal process-derived structures, characterized by median cleft, nasal anomalies, widely spaced eyes, and cranium bifidum occultum. Several entities of syndromic frontonasal dysplasia have been described, among which, to date, only a few have identified molecular bases. We clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. We identified six individuals with a similar phenotype, including one discordant monozygous twin. Facial features were remarkable by nasal deformity with creased ridge and depressed or absent tip, widely spaced eyes, almond-shaped palpebral fissures, and downturned corners of the mouth. All had apparently normal psychomotor development. In addition, upper limb anomalies, frontonasal encephalocele, corpus callosum agenesis, choanal atresia, and congenital heart defect were observed. We identified five reports in the literature of patients presenting with the same phenotype. Exome sequencing was performed on DNA extracted from blood of two individuals, no candidate gene was identified. In conclusion, we report six novel simplex individuals presenting with a specific frontonasal dysplasia entity associating recognizable facial features, limb and visceral malformations, and apparently normal development. The identification of discordant monozygotic twins supports the hypothesis of a mosaic disorder. Although previous patients have been reported, this is the first series, allowing delineation of a clinical subtype of frontonasal dysplasia, paving the way toward the identification of its molecular etiology.

Bohring–Opitz syndrome (BOS) was first described by Bohring et al. [1999]. The authors reported four cases which had several features in common, including a prominent metopic suture, hypertelorism, exophthalmos, cleft lip and palate, limb anomalies, as well as difficulty feeding with severe developmental delays. In almost 50% of cases that meet the clinical criteria for BOS, de novo frameshift and nonsense mutations in the ASXL1 gene have been detected, suggesting that loss of function of this gene is a major cause. We report on the clinical characterization of one young female patient who was evaluated because of severe developmental delays, failure to thrive, and multiple minor anomalies and was clinically diagnosed with BOS. Whole exome sequencing analysis detected one novel disruptive frameshift mutation in the ASXL1 gene and we were also able to confirm the presence of two CFTR mutations associated with her chronic pancreatitis with acute severe breakthrough attacks requiring multiple ICU admissions. This latter complication of pancreatitis further contributed to the complexity of the clinical presentation and represents an independent genetic finding. Our case report emphasizes the importance of highly specific phenotypic characterization of patients with complex phenotypes before proceeding with molecular studies. That approach will lead to more accurate molecular data interpretation and better clinical genetic diagnosis, particularly for those patients with rare, difficult-to-diagnose disorders.