About

Jennifer M. Kalish, MD, PhD, is an Assistant Professor of Pediatrics (Human Genetics) at the University of Pennsylvania's Perelman School of Medicine. She is an attending physician in the Division of Genetics at Children's Hospital of Philadelphia and a research scientist at the Center for Childhood Cancer Research at the same hospital. Dr. Kalish serves as the Director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia and is the Director of the Program of Excellence in Beckwith-Wiedemann Syndrome at the University of Pennsylvania's Orphan Disease Center. She is a member of the Abramson Cancer Center at the University of Pennsylvania and holds the Lorenzo “Turtle” Sartini Jr Endowed Chair in Beckwith-Wiedemann Syndrome Research.

Research topics

• Medicine
• Biology
• Genetics
• Pediatrics
• Internal medicine

Selected publications

• Phenotype Expansion of Malan Syndrome: New Cases and a Review of the Literature

  American Journal of Medical Genetics Part A · 2026-04-03

  articleOpen accessSenior authorCorresponding

  Malan syndrome is an ultra-rare overgrowth syndrome caused by pathogenic variants or deletions in nuclear factor one X (NFIX) located at 19p13.2. Here, we report a comprehensive literature review and phenotyping of known patients with Malan syndrome and present a novel cohort of eight patients. This report further establishes the common characteristics of Malan syndrome, expands the ophthalmologic features and airway distress phenotypes, and provides updated management recommendations.

  PublisherDOI

• A mixed methods study of the impact of WAGR spectrum disorder on individuals and their caregivers

  Orphanet Journal of Rare Diseases · 2026-04-24

  articleOpen accessSenior author

  WAGR spectrum disorder (WSD) is a rare genetic condition classically characterized by Wilms tumor, Aniridia, Genitourinary abnormalities, and Range of developmental delay. Following our publication, the terminology has shifted from “syndrome” to “spectrum disorder” to better capture its phenotypic variability.1 While other multi-systemic features have been identified, there is a paucity of literature around how WSD impacts individuals and their families. To guide clinical management recommendations and development of outcome measures for WSD clinical studies, this study explored the lived experiences of children with WSD and their caregivers. Fourteen caregivers to 13 children with WSD participated in this two-part study, consisting of a survey that collected medical information for each child with WSD and semi-structured interviews that focused on how WSD impacts daily life. Survey data were analyzed using descriptive statistics. Interview data were analyzed using reflexive thematic analysis within a critical realism framework. Aniridia was the most frequently reported health condition, although a broad range of co-occurring conditions exemplified clinical heterogeneity of WSD. Analysis of caregiver interviews generated five key themes: (1) uncertainty has a profound emotional impact on caregivers, (2) while the prospect of lifelong caregiving is stressful, caring for a child with WSD is rewarding, (3) partnerships between healthcare providers and families are critical, (4) three areas to prioritize for assessment in future WSD clinical studies include aniridia/vision, behavioral/psychiatric, and speech/communication conditions, and (5) the WSD community is a powerful support system. This study offers valuable insight into the multifaceted impacts of WSD on individuals and their caregivers. Our findings highlight key therapeutic targets and opportunities to improve clinical care and support for the WSD community.

  PublisherDOI

• Beckwith-Wiedemann syndrome multiomic analysis of hepatoblastoma uncovers unique tumour heterogeneity and cellular landscapes, including transition cells leading to tumour formation

  BJC Reports · 2026-05-20

  articleOpen accessSenior author

  BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth and cancer predisposition syndrome caused by epigenetic alterations on chromosome 11p15 that predisposes children to multiple cancer types, including hepatoblastoma. Hepatoblastoma is heterogenous in nature, and the 11p15 changes that cause BWS can also be found as a somatic alteration in nonBWS hepatoblastomas, further adding complexity to this disease. METHODS: To understand the impact of the predisposition molecular cues in BWS hepatoblastoma, we interrogated BWS and nonBWS hepatoblastomas, as well as adjacent normal liver, using a multiomic approach [single nuclei RNA-sequencing (snRNA-seq) + single nuclei assay for transposable-accessible chromatin sequencing (snATAC-seq)]. RESULTS: Our approach identified an enrichment of the WNT signaling pathway in BWS hepatoblastoma. Despite similar histology, we found greater tumour heterogeneity and embryonic transcriptional signatures in BWS hepatoblastoma. Furthermore, using pseudotime analysis, we identified a population of transition cells in BWS, with unique molecular profiles, which likely promote the precancer to cancer neoplastic transition in BWS. CONCLUSIONS: This study highlights key signaling pathways, particularly WNT, and identifies a unique population of intermediate/transition cells that may drive neoplastic transformation in BWS hepatoblastoma. These findings provide new insights into the molecular events leading to cancer in BWS and suggest potential targets for early intervention and prevention strategies.

  PublisherOA PDFDOI

• Functional evaluation of pancreatic islets from patients with Beckwith–Wiedemann syndrome and congenital hyperinsulinism

  The Journal of Clinical Endocrinology & Metabolism · 2026-02-06

  articleOpen access

  CONTEXT: Beckwith-Wiedemann Syndrome (BWS) is an overgrowth syndrome caused by various genetic or epigenetic abnormalities in a cluster of imprinted genes on chromosome 11p15. Congenital hyperinsulinism (HI) is one of the cardinal features of BWS, but the pathophysiology of HI in BWS has not been clearly defined. OBJECTIVE: We describe the islet phenotype of a series of infants with severe HI and comorbid BWS who required pancreatectomy for intractable hypoglycemia. METHODS: The cases are a subset of HI patients who required pancreatectomy and had Beckwith-Wiedemann Syndrome. Molecular testing for BWS was performed by SNP array and chromosome 11p15 methylation analysis. Functional analysis of insulin secretion in pancreatic islets isolated from pancreatectomy samples was completed with perifusion experiments and cytosolic Ca2+ measurements. RESULTS: Similar to what we had previously described in islets isolated from the pancreas of infants with HI due to inactivating mutations in the KATP channel, BWS-HI islets have elevated concentrations of cytosolic calcium and secrete insulin in response to stimulation with a physiologic mixture of amino acids. However, unlike KATPHI islets, most BWS-HI islets retain responsiveness to stimulation with glucose and the KATP channel inhibitor glyburide. Through RNAseq analysis, we observed that expression of KCNQ1, encoding the pore-forming subunit of a voltage-gated K+ channel (Kv7.1), is reduced in BWS-HI islets compared to normal human islets (3-fold; p = 4.5 x 10-7). CONCLUSIONS: Our expression analysis and functional evaluation of islets isolated from BWS-HI patients reveal the spectrum of insulin secretion responses found across BWS etiologies and suggest a potential role for loss of KCNQ1 expression in the complex pathophysiology responsible for the hyperinsulinism in BWS.

  PublisherDOI

• Determinants of hyperinsulinism severity in children with Beckwith-Wiedemann syndrome

  The Journal of Clinical Endocrinology & Metabolism · 2026-02-06 · 1 citations

  articleSenior author

  CONTEXT: Congenital hyperinsulinism (HI) is a serious clinical feature of Beckwith-Wiedemann syndrome (BWS) causing severe hypoglycemia. The relationship between BWS genotypes and HI severity is not well understood. OBJECTIVE: Investigate the relationship between molecular determinants of patients with BWS and HI with measures of HI severity. DESIGN: Retrospective cohort study including 85 children from 2009-2024. SETTING: All patients evaluated at single, tertiary care center. PATIENTS: BWS genotype frequency included 41 children with pUPD11, 24 with IC2 LOM, eight with 11p15 chromosomal anomalies, six with GWpUPD, four with IC1 GOM, and two with CDKN1C. INTERVENTIONS: Retrospectively reviewed interventions included maximum glucose infusion rate (max GIR), diazoxide responsiveness, and surgery. MAIN OUTCOME MEASURES: Primary outcome was association between BWS genotypes and measures of HI severity. Secondary outcomes included the relationship between pUPD11 length and presence of K-ATP variants with diazoxide responsiveness and surgical need. RESULTS: Significant differences presented among genotypes in max GIR (p = 0.004), enteral dextrose requirements (p = 0.029), and pancreatectomy (p = 0.012). Most patients with IC2 LOM, IC1 GOM or CDKN1C were diazoxide responsive and did not require surgery. Patients with pUPD11 were more likely to be diazoxide unresponsive and require surgery, especially if pUPD11 length extended into the K-ATP gene region and if a pathogenic variant in the ABCC8 or KCNJ11 was present. CONCLUSION: Patients with pUPD11 experience more severe HI, while patients with IC2 LOM, IC1 GOM, and CDKN1C exhibit milder disease. Based on our findings, we designed a genetic testing algorithm to guide clinical management.

  PublisherDOI

• Supplemental data from: Determinants of hyperinsulinism severity in children with Beckwith-Wiedemann Syndrome

  Open MIND · 2026-01-08

  datasetSenior author

  Context: Congenital hyperinsulinism (HI) is a serious clinical feature of Beckwith-Wiedemann syndrome (BWS) causing severe hypoglycemia. The relationship between BWS genotypes and HI severity is not well understood. Objective: Investigate the relationship between molecular determinants of patients with BWS and HI with measures of HI severity. Design: Retrospective cohort study including 85 children from 2009-2024. Setting: All patients evaluated at single, tertiary care center. Patients: BWS genotype frequency included 41 children with pUPD11, 24 with IC2 LOM, eight with 11p15 chromosomal anomalies, six with GWpUPD, four with IC1 GOM, and two with CDKN1C. Interventions: Retrospectively reviewed interventions included maximum glucose infusion rate (max GIR), diazoxide responsiveness, and surgery. Main Outcome Measures: Primary outcome was association between BWS genotypes and measures of HI severity. Secondary outcomes included the relationship between pUPD11 length and presence of K-ATP variants with diazoxide responsiveness and surgical need. Results: Significant differences presented among genotypes in max GIR (p = 0.004), enteral dextrose requirements (p = 0.029), and pancreatectomy (p = 0.012). Most patients with IC2 LOM, IC1 GOM or CDKN1C were diazoxide responsive and did not require surgery. Patients with pUPD11 were more likely to be diazoxide unresponsive and require surgery, especially if pUPD11 length extended into the K-ATP gene region and if a pathogenic variant in the ABCC8 or KCNJ11 was present. Conclusion: Patients with pUPD11 experience more severe HI, while patients with IC2 LOM, IC1 GOM, and CDKN1C exhibit milder disease. Based on our findings, we designed a genetic testing algorithm to guide clinical management.

  DOI

• Patient-Reported Speech Outcomes in Patients with Beckwith-Wiedemann Syndrome

  Plastic & Reconstructive Surgery · 2026-03-10

  article

  BACKGROUND: Macroglossia is a hallmark feature of Beckwith-Wiedemann Syndrome (BWS) and may affect a child's appearance, speech, and feeding. Tongue reduction surgery (TRS) is often recommended to address functional concerns, but its effects on patient-reported speech outcomes remain unclear. This study evaluates self-reported speech outcomes in individuals with BWS. METHODS: Patients with BWS (aged 4-18 years) were prospectively administered the FACE-Q Craniofacial measures (speech distress, breathing, eating and drinking, facial function, speech function). Surveys were Rasch transformed score (0-100, 100=best outcome). Clinical characteristics, BWS Index of Macroglossia (BIG), and Intelligibility in Context Scale (ICS) scores were reviewed. RESULTS: Thirty-six patients (50% male; mean age 8.6±3.8 years at survey) were included. Most patients had an IC2-LOM genetic diagnosis (n=24, 66.6%). Average BIG score was 1.3±1.1 (range 0-3). Speech therapy was received by 28 patients (77.8%) and 16 (44.4%) underwent TRS at mean age 2.3±2.0 years. FACE-Q scores averaged 84.7±15.0 for speech distress, 84.9±15.0 for breathing, 80.9±15.9 for eating and drinking, 92.0±12.1 for facial function, and 75.8±19.5 for speech function. There was moderate correlation between ICS score and speech function (r=0.697, p=0.001). Patients who received speech therapy at school and clinically had lower speech function (p=0.014). No significant differences were found between surgical and non-surgical patients or by BIG scores (p>0.1). CONCLUSIONS: While overall reported outcomes were favorable, speech function scores were lower, suggesting persistent speech challenges in this population. These findings underscore the multifactorial nature of speech development in BWS and the importance of individualized, longitudinal management to optimize outcomes.

  PublisherDOI

• High‐Resolution Genomic Characterization of <scp>WAGR</scp> Spectrum Disorder: Insights From a Novel Cohort and Literature Synthesis, and Validation of Patient‐Reported Data

  American Journal of Medical Genetics Part A · 2026-04-12

  articleOpen accessSenior author

  WAGR spectrum disorder (WAGRSD) is an ultra-rare congenital disorder caused by heterozygous deletion of chromosome 11p13. While classically associated with Wilms tumor, Aniridia, Genitourinary anomalies, and a Range of developmental delays, accurate delineation of the deletion is critical for prognosis because the phenotypic spectrum extends well beyond this tetrad. To improve diagnostic resolution, we developed and validated a high-density custom CGH-SNP array for precise breakpoint mapping of 11p13. We present a molecularly confirmed cohort of 23 new patients and integrate these with 91 published cases, forming the largest combined cohort to date (N = 114) with detailed genotype-phenotype information. Key findings include: (1) the custom array provided superior genomic resolution compared to standard clinical arrays; (2) seven patients (6.1%) were found to have a dual diagnosis of WAGRSD and Potocki-Shaffer syndrome (PSS)-a contiguous-gene syndrome characterized by multiple osteochondromas that requires distinct surveillance; (3) in 42 patients with fully defined deletions (n = 42, 38% of the cohort), no statistically significant association was observed between deletion of LMO2 (or other candidate genes) and Wilms tumor risk; and (4) phenotypic frequencies in this medically validated cohort closely aligned with prior caregiver-reported registry data, validating patient-driven registries as a reliable resource for rare disease research. Together, these findings underscore the necessity of high-resolution genomic testing to guide counseling, refine anticipatory management-including screening for PSS-related complications-and expand the phenotypic understanding of 11p13 deletion disorders.

  PublisherDOI

• P722: Clinical features indicative of positive genetic test outcome in a series of prenatal cases of Beckwith-Wiedemann syndrome

  Genetics in Medicine Open · 2026-01-01

  articleOpen access
  PublisherDOI

• Myogenic dysregulation underlies tongue overgrowth in Beckwith-Wiedemann syndrome

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-20

  articleOpen accessSenior authorCorresponding

  Summary Macroglossia is a clinically significant feature of Beckwith-Wiedemann syndrome (BWS), but the cellular basis of tongue overgrowth remains poorly defined. Here, using pediatric tongue specimens from molecularly defined BWS subtypes and age-matched nonBWS controls, we show that BWS macroglossia is characterized by skeletal muscle fiber hypertrophy rather than increased fiber number. This phenotype is not explained by expansion or increased proliferation of satellite cells in situ , and prospectively isolated tongue satellite cells do not exhibit enhanced proliferation under growth conditions in vitro . Instead, BWS progenitors adopt distinct differentiation-associated regulatory states. IC2 loss of methylation cells sustain proliferative activity during differentiation and form enlarged myotubes, consistent with a cell-autonomous hypertrophic program. In contrast, pUPD11 cells display activation of NOTCH signaling and progenitor-associated programs, together with attenuated progression toward terminal myogenic differentiation. These findings identify skeletal muscle hypertrophy as a core tissue-level feature of BWS macroglossia and reveal that epigenetically defined BWS subtypes engage divergent myogenic programs that converge on a shared hypertrophic tissue phenotype. Together, these data define subtype-specific myogenic states in a rare human disease tissue and provide a framework for understanding how distinct epigenetic changes can produce a common overgrowth phenotype. Highlights BWS macroglossia is associated with skeletal muscle fiber hypertrophy, not fiber hyperplasia Tongue satellite cell abundance and proliferation are not increased in situ in BWS IC2 loss of methylation cells sustain proliferation during differentiation and form enlarged myotubes pUPD11 cells show enhanced NOTCH signaling and a constrained myogenic state In brief Tichy et al. show that Beckwith-Wiedemann syndrome macroglossia is driven by skeletal muscle hypertrophy and that distinct BWS molecular subtypes engage different myogenic regulatory programs. IC2 loss of methylation cells sustain proliferation during differentiation, whereas pUPD11 cells exhibit NOTCH-associated restraint of myogenic progression.

  PublisherOA PDFDOI

Recent grants

• The Mechanism of Tumor Formation in Beckwith-Wiedemann Syndrome

  NIH · $703k · 2015–2021

Frequent coauthors

• Kelly A. Duffy

  Children's Hospital of Philadelphia

  66 shared

• Jesse A. Taylor

  Children's Hospital of Philadelphia

  48 shared

• Evan R. Hathaway

  Children's Hospital of Philadelphia

  34 shared

• Matthew A. Deardorff

  California University of Pennsylvania

  33 shared

• Arupa Ganguly

  University of Pennsylvania

  29 shared

• Christopher M. Cielo︎

  Children's Hospital of Philadelphia

  25 shared

• Elaine H. Zackai

  Children's Hospital of Philadelphia

  25 shared

• Lisa J. States

  University of Pennsylvania

  24 shared

Labs

• Kalish LabPI

Awards & honors

• Lorenzo “Turtle” Sartini Jr Endowed Chair, Beckwith-Wiedeman…