- Clinical Genetics
Clinical Assistant Professor, Pediatrics - Medical Genetics
Board Certification: American Board of Pediatrics, Pediatrics (2018)
Board Certification, American Board of Pediatrics, Pediatrics (2018)
Board Certification: American Board of Medical Genetics and Genomics, Clinical Genetics (2017)
Fellowship: Children's Hospital of Philadelphia (2017) PA
Residency: Children's Hospital of Philadelphia (2016) PA
Internship: Children's Hospital of Philadelphia (2014) PA
Medical Education: Jefferson Medical College (2013) PA
De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities.
Journal of medical genetics
Whole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies.To discover novel genes linked to both CC anomalies and NDD.Clinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared.We identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging.Our findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.
View details for DOI 10.1136/jmedgenet-2019-106193
View details for PubMedID 31924697
Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study.
Orphanet journal of rare diseases
2020; 15 (1): 336
Mucopolysaccharidosis (MPS) IVA, also known as Morquio A syndrome, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase. Early recognition, diagnosis, and treatment of this progressive, multisystem disease by enzyme replacement therapy (ERT) can lead to improved outcomes and reduced mortality.This report documents the diagnostic journey and treatment with ERT of three siblings with MPS IVA. Clinical outcome measures included growth, endurance, imaging, cardiac, respiratory, ophthalmology, and laboratory evaluations.Three siblings, diagnosed at 14.7, 10.1, and 3.2 years of age, demonstrated clinical improvement with weekly infusions of 2.0 mg/kg elosulfase alfa (Vimizim®, BioMarin Pharmaceutical, Novato, CA, USA). Patient 1 (oldest sibling) and Patient 2 (middle sibling) experienced a diagnostic delay of 8 years 7 months and 4 years after symptom onset, respectively. All three patients demonstrated improvements in growth, 6-min walk distance, joint range of motion, and respiratory function after 30 months of ERT. The treatment was well tolerated without any adverse events.This case series highlights the importance of early recognition of the clinical and imaging findings that are initially subtle in MPS IVA. Early treatment with ERT is necessary to slow irreversible disease progression and improve patient outcomes. The oldest sibling experienced improvements in mobility despite severe symptoms resulting from a late diagnosis. When evaluating patients with skeletal anomalies, imaging multiple body regions is recommended. When findings such as anterior beaking of vertebrae or bilateral femoral head dysplasia are present, MPS IVA should be included in the differential diagnosis. Newborn screening must be considered for early detection, accurate diagnosis, and initiation of treatment to reduce morbidity.
View details for DOI 10.1186/s13023-020-01618-y
View details for PubMedID 33256811
- ClinPhen extracts and prioritizes patient phenotypes directly from medical records to expedite genetic disease diagnosis GENETICS IN MEDICINE 2019; 21 (7): 1585–93
LOCALIZING NEUROLOGIC FEATURES AT PRESENTATION OF VLCAD DEFICIENCY
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2019: 282
View details for Web of Science ID 000483451500104
Paraspinal Atrophy Suggesting Underlying Genetic Etiology
LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965901365
LOCALIZING NEUROLOGIC FEATURES AT PRESENTATION OF VLCAD DEFICIENCY
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2019: 311
View details for Web of Science ID 000463310000117
THE DIAGNOSIS AND NATURAL HISTORY OF THE MUCOPOLYSACCHARIDOSIS IVA IN ONE FAMILY
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2018: 249–50
View details for Web of Science ID 000428001200108
- The diagnosis and natural history of mucopolysaccharidosis type IVA in one family ACADEMIC PRESS INC ELSEVIER SCIENCE. 2018: S92
ClinPhen extracts and prioritizes patient phenotypes directly from medical records to expedite genetic disease diagnosis.
Genetics in medicine : official journal of the American College of Medical Genetics
Diagnosing monogenic diseases facilitates optimal care, but can involve the manual evaluation of hundreds of genetic variants per case. Computational tools like Phrank expedite this process by ranking all candidate genes by their ability to explain the patient's phenotypes. To use these tools, busy clinicians must manually encode patient phenotypes from lengthy clinical notes. With 100 million human genomes estimated to be sequenced by 2025, a fast alternative to manual phenotype extraction from clinical notes will become necessary.We introduce ClinPhen, a fast, high-accuracy tool that automatically converts clinical notes into a prioritized list of patient phenotypes using Human Phenotype Ontology (HPO) terms.ClinPhen shows superior accuracy and 20× speedup over existing phenotype extractors, and its novel phenotype prioritization scheme improves the performance of gene-ranking tools.While a dedicated clinician can process 200 patient records in a 40-hour workweek, ClinPhen does the same in 10 minutes. Compared with manual phenotype extraction, ClinPhen saves an additional 3-5 hours per Mendelian disease diagnosis. Providers can now add ClinPhen's output to each summary note attached to a filled testing laboratory request form. ClinPhen makes a substantial contribution to improvements in efficiency critically needed to meet the surging demand for clinical diagnostic sequencing.
View details for PubMedID 30514889