Rapid Transition to Telemedicine During the COVID-19 Pandemic: Medical Genetics Experience.

BACKGROUND: The coronavirus SARS-CoV-2 (COVID-19) pandemic interrupted delivery of outpatient health care to minimize risk of exposure. This pandemic threatened to increase longstanding national concerns about access to both initial and follow-up genetics clinics services. The Medical Genetics Clinic at the University of Wisconsin-Madison Waisman Center (WCMGC) rapidly transitioned to offering appointments using telemedicine in March 2020 when the public health emergency for COVID-19 pandemic was declared. METHODS: Datasets were reviewed for the periods April - July 2019 (pre-COVID baseline) and April - July 2020 (COVID project data). Patient schedules were accessed to determine the number of appointments kept, no-shows, and late cancellations. A telephone survey was utilized to assess patient satisfaction with telemedicine. RESULTS: Fewer appointments were missed and providers completed more clinic visits after transitioning to telemedicine. Patients and their families were equally satisfied with care received and were amenable to telemedicine use in the future. Telemedicine allowed WCMGC to continue serving patients during a period of restricted on-site services, suggesting its continuation would improve access to genetic services.

Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation.

Pathogenic allelic variants in the fibroblast growth factor receptor 3 (FGFR3) gene have been associated with a number of phenotypes including achondroplasia, hypochondroplasia, thanatophoric dysplasia, Crouzon syndrome with acanthosis nigricans (Crouzonodermoskeletal syndrome), and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans). Crouzon syndrome with acanthosis nigricans is caused by the pathogenic variant c.1172C>A (p.Ala391Glu) in the FGFR3 gene. The p.Lys650Thr pathogenic variant in FGFR3 has been linked to acanthosis nigricans without significant craniofacial or skeletal abnormalities. Recently, an infant with achondroplasia and a novel p.Ser348Cys FGFR3 mutation was reported. We describe the clinical history of an 8-year-old child with a skeletal dysplasia in the achondroplasia-hypochondroplasia spectrum, acanthosis nigricans, typical development, and the recently described p.Ser348Cys FGFR3 mutation.

A 137-kb deletion within the Potocki-Shaffer syndrome interval on chromosome 11p11.2 associated with developmental delay and hypotonia.

Potocki-Shaffer syndrome (PSS) is a rare disorder caused by haploinsufficiency of genes located on the proximal short arm of chromosome 11 (11p11.2p12). Classic features include biparietal foramina, multiple exostoses, profound hypotonia, dysmorphic features, and developmental delay/intellectual disability. Fewer than 40 individuals with PSS have been reported, with variable clinical presentations due in part to disparity in deletion sizes. We report on a boy who presented for initial evaluation at age 13 months because of a history of developmental delay, hypotonia, subtle dysmorphic features, and neurobehavioral abnormalities. SNP microarray analysis identified a 137 kb deletion at 11p11.2, which maps within the classically defined PSS interval. This deletion results in haploinsufficiency for all or portions of six OMIM genes: SLC35C1, CRY2, MAPK8IP1, PEX16, GYLTL1B, and PHF21A. Recently, translocations interrupting PHF21A have been associated with intellectual disability and craniofacial anomalies similar to those seen in PSS. The identification of this small deletion in a child with developmental delay and hypotonia provides further evidence for the genetic basis of developmental disability and identifies a critical region sufficient to cause hypotonia in this syndrome. Additionally, this case illustrates the utility of high resolution genomic approaches in correlating clinical phenotypes with specific genes in contiguous gene deletion syndromes.

A novel STXBP1 mutation causes focal seizures with neonatal onset.

Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with severe infantile epileptic encephalopathies (Ohtahara syndrome and West syndrome), but also with moderate to severe cognitive impairment and nonsyndromic epilepsy. We have studied a white infant who presented with focal seizures at age 2 weeks. Brain imaging was unremarkable. The electroencephalograph (EEG) demonstrated normal background frequency content but with multifocal sharp waves and no evidence of the typical patterns associated with Ohtahara or West syndrome. Therapy with levetiracetam and oxcarbazepine effectively managed the seizure episodes. Investigation of genes associated with infantile forms of epilepsy such as SCN1A, SCN1B, and ARX were negative, but we identified a novel single-nucleotide duplication mutation, c.931dupT (p.S311FfsX3), in exon 11 of the STXBP1 gene. This previously unreported STXBP1 mutation in a subject with neonatal-onset focal seizures broadens the spectrum of clinically relevant human disorders caused by STXBP1 mutations.