TAOK1 is associated with neurodevelopmental disorder and essential for neuronal maturation and cortical development.

Thousand and one amino-acid kinase 1 (TAOK1) is a MAP3K protein kinase, regulating different mitogen-activated protein kinase pathways, thereby modulating a multitude of processes in the cell. Given the recent finding of TAOK1 involvement in neurodevelopmental disorders (NDDs), we investigated the role of TAOK1 in neuronal function and collected a cohort of 23 individuals with mostly de novo variants in TAOK1 to further define the associated NDD. Here, we provide evidence for an important role for TAOK1 in neuronal function, showing that altered TAOK1 expression levels in the embryonic mouse brain affect neural migration in vivo, as well as neuronal maturation in vitro. The molecular spectrum of the identified TAOK1 variants comprises largely truncating and nonsense variants, but also missense variants, for which we provide evidence that they can have a loss of function or dominant-negative effect on TAOK1, expanding the potential underlying causative mechanisms resulting in NDD. Taken together, our data indicate that TAOK1 activity needs to be properly controlled for normal neuronal function and that TAOK1 dysregulation leads to a neurodevelopmental disorder mainly comprising similar facial features, developmental delay/intellectual disability and/or variable learning or behavioral problems, muscular hypotonia, infant feeding difficulties, and growth problems.

Ehlers-Danlos syndrome: what the radiologist needs to know.

Ehlers-Danlos syndrome is a real diagnosis that is erroneously used to explain multiple fractures in suspected child abuse. This paper reviews the clinical and molecular diagnostic criteria for Ehlers-Danlos syndrome. This knowledge can help prevent misdiagnosis and support clinicians when evaluating infants and young children with multiple fractures.

Genetic causes of fractures and subdural hematomas: fact versus fiction.

Genetic disorders are in the differential diagnosis when young children present with unexplained fractures or intracranial hemorrhage. For medical and legal reasons, it is imperative to make the correct diagnosis and provide clear, evidence-based explanations of how alternative diagnoses were ruled out. A genetics consultation in cases of suspected child physical abuse should synthesize the history of present illness, medical history, family history, physical examination, and radiologic and laboratory findings in consultation with other specialists. The medical geneticist highlights how these disorders truly present. When the natural history of a genetic disorder is understood, it becomes clear that genetic disorders are not mysterious or difficult to diagnose. As highlighted in this case-based review, mainstream medical practice allows for differentiation among the intracranial and skeletal manifestations of osteogenesis imperfecta, Menkes disease, glutaric acidemia type 1 and child physical abuse. This review also highlights how a genetic disorder, Ehlers-Danlos syndrome, can be misused in a courtroom. Finally, this review summarizes when genetic testing is appropriate in cases of suspected child physical abuse.

Direct-to-patient telemedicine: Expanding access to regional pediatric specialty care.

Telemedicine is seen as a useful tool in reducing gaps in health care but this technology-enabled care can also exacerbate health inequity if not implemented with a focus on inclusivity. Though many studies have reported improvements as well as exacerbation of disparities in access to care in their telehealth programs, there does not exist a common evaluation tool to assess these programs. To mitigate the impact of COVID-19 on health care workers and protect medically vulnerable children, in March 2020 we expanded our pre-established specialty and subspecialty direct-to-patient pediatric telemedicine program in a high volume urban pediatric health system. Our program aimed to prevent disparities in pediatric health care. In this study, using a "Pillars of Access" approach as a model to evaluate impact and access to care of our direct-to-patient telemedicine program, we analyzed the patients that were seen pre-COVID versus post-COVID. Our study demonstrated an increase in telemedicine visits for patients from diverse socioeconomic and racial backgrounds, and geographically underserved communities. We also observed an increase in telemedicine visits for mental health complaints and for certain categories of high-risk patients. This study was not designed to identify language and cultural barriers to telemedicine. Future identification of these specific barriers is needed. The tool to evaluate telehealth impact/access to care through a "Pillars of Access" approach presented here could serve as a model for implementation of telehealth programs. Our study highlights telemedicine programs as a mechanism to address healthcare inequity and overcome barriers to care.