About

Beverly S. Emanuel, PhD, is the Charles E.H. Upham Professor of Pediatrics at the University of Pennsylvania's Perelman School of Medicine, affiliated with the Department of Pediatrics. His research expertise centers on human genetics, specifically investigating diseases caused by abnormalities of human chromosomes, with a particular focus on chromosome 22. Dr. Emanuel has contributed to understanding the genetic basis of developmental abnormalities and mental retardation associated with chromosomal deletions and duplications, including DiGeorge Syndrome (DGS) and Velocardiofacial Syndrome (VCFS). He has helped develop standard diagnostic tests used worldwide to detect chromosomal deletions and assess recurrence risks. His laboratory conducts molecular analyses of deletion and translocation breakpoint regions, including the recurrent t(11;22) translocation, where he has identified unusual DNA structures that suggest mechanisms for chromosomal instability. His work involves techniques such as fluorescence in situ hybridization, PCR, Southern blot, and pulsed-field gel electrophoresis to elucidate the etiology of various chromosomal disorders.

Research topics

• Biology
• Genetics
• Medicine
• Molecular biology
• Psychology

Selected publications

• 22q11.2 Deletion Syndrome in Offspring Conceived via Assisted Reproductive Technology Versus Spontaneously

  Genes · 2026-01-06

  articleOpen access

  Background/Objectives: The majority of chromosome 22q11.2 deletions are de novo, resulting from meiotic non-allelic homologous recombination (NAHR). While 22q11.2 deletion syndrome (22q11.2DS)-associated phenotypes are well characterized, risk factors leading to NAHR are poorly understood, including the possible relationship with assisted reproductive technology (ART). Here we examined the prevalence of ART conceptions and medical comorbidities in patients with 22q11.2DS vs. spontaneously conceived (SC) patients with 22q11.2DS. Methods: Retrospective analysis, under IRB approval, of medical records on 1184 patients with laboratory-confirmed de novo chromosome 22q11.2 deletions was performed. ART conceptions included IVF with and without ICSI. Deletion size and obstetric, family, and medical histories were examined. Results: We identified 30 pregnancies conceived using ART (2.57%) compared with the U.S. general population rate of 2.3% (p-value = 0.6603). ART and SC sub-cohorts demonstrated no significant differences in deletion size or perinatal outcomes, including preterm birth, multiples, polyhydramnios, or congenital heart disease. Controlling for these factors, neonates conceived via ART were more likely to be admitted to the ICU (aOR = 6.3). Conclusions: Pregnancies conceived via ART, and later found to have 22q11.2DS, demonstrated no significant differences in prevalence or perinatal outcomes compared with the U.S. general population. Moreover, NAHR is unrelated to ART in this population. Likewise, associated phenotypic features are unrelated. These data will be reassuring to those families where ART was employed to conceive children who were later found to have 22q11.2DS.

  PublisherOA PDFDOI

• Genome-wide tandem repeat expansions modify schizophrenia risk in the presence of a 22q11.2 deletion

  Molecular Psychiatry · 2026-04-15

  articleOpen access

  Schizophrenia develops in one in every four individuals with a pathogenic 22q11.2 deletion, yet the genetic modifiers influencing the manifestation of schizophrenia in this high-risk group remain incompletely understood. Here, we identify rare tandem repeat expansions (TREs) as significant contributors to schizophrenia risk in this population. Genome sequencing of 438 unrelated individuals with 22q11.2 deletions revealed a marked enrichment of rare genic TREs among those with schizophrenia, with effect sizes comparable to common polygenic risk. These TREs are disproportionately located in intronic and splice-adjacent regions relative to other genomic regions, with evidence suggesting that they disrupt gene regulation through mechanisms including altered methylation and splicing. Cell-type-specific analyses indicate that TREs are primarily associated with differentially expressed genes in excitatory and inhibitory neurons in the prefrontal cortex. Affected genes, including DLGAP2 and DMPK, are involved in neurodevelopment and synaptic organization. These findings extend the role of TREs as genetic modifiers, providing new insights into the molecular mechanisms underlying schizophrenia in this ultra-high-risk population and into the broader biology of idiopathic schizophrenia.

  PublisherOA PDFDOI

• Prevalence and Spectrum of Congenital Heart Disease in Individuals With Distal Chromosome 22q11.22–23 Deletions

  Clinical Genetics · 2025-12-08

  articleOpen access

  This study is aimed at determining the spectrum of congenital heart disease associated with distal 22q11.22-23 deletions flanked by low copy repeats, LCR22 D-H. We analyzed cardiology findings in 128 unrelated individuals with distal LCR22 D-H deletions. A total of 62 were newly described and 66 were derived from previous reports. We found that deletions which included LCR22-D as the proximal endpoint were the most prevalent in the cohort (104/128, 81.3%). Clinically relevant congenital heart disease was identified in 48 individuals (37.5%, 95% CI 29%-46%), which is lower than the prevalence reported for typical, proximal LCR22 A-D deletions (p = 3.7E-4), especially for conotruncal defects (13/128, 10.2%; p = 7.1E-13). Mild to moderate CHD predominated, including ventricular septal defects (22/128), bicuspid aortic valve (9/128) and mild cardiomyopathy (3/128). Persistent truncus arteriosus was the most prevalent (n = 8/13) conotruncal heart defect, but other anomalies also occurred in singleton cases. These findings support the need for cardiac evaluation in all individuals with distal 22q11.22-23 deletions, increased use of clinical genetic testing in syndromic individuals with these findings, and molecular studies in model systems. The results demonstrate that reduced gene dosage of distal 22q11.21-23, particularly within the D-E region including MAPK1 and HIC2 convey risk for CHD.

  PublisherOA PDFDOI

• Prevalence and spectrum of congenital heart disease in individuals with distal chromosome 22q11.22-23 deletions

  medRxiv · 2025-10-19

  preprintOpen access

  ABSTRACT This study is aimed to determine the spectrum of congenital heart disease associated with distal 22q11.22-23 deletions flanked by low copy repeats, LCR22 D-H. We analyzed cardiology findings in 128 unrelated individuals with distal LCR22 D-H deletions. A total of 62 were newly described and 66 were derived from previous reports. We found that deletions which included LCR22-D as the proximal endpoint were the most prevalent in the cohort (104/128, 81.3%). Clinically relevant congenital heart disease was identified in 48 individuals (37.5%, 95% CI 29-46%), which is lower than the prevalence reported for typical, proximal LCR22 A-D deletions (p=3.7E-4), especially for conotruncal defects (13/128, 10.2%; p=7.1E-13). Mild to moderate CHD predominated, including ventricular septal defects (22/128), bicuspid aortic valve (9/128) and mild cardiomyopathy (3/128). Persistent truncus arteriosus was the most prevalent (n=8/13) conotruncal heart defect, but other anomalies also occurred in singleton cases. These findings support the need for cardiac evaluation in all individuals with distal 22q11.22-23 deletions, increased use of clinical genetic testing in syndromic individuals with these findings, and molecular studies in model systems. The results demostrate that reduced gene dosage of distal 22q11.21-23, particularly within the D-E region including MAPK1 and HIC2 convey risk for CHD.

  PublisherOA PDFDOI

• ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome

  Nature Cell Biology · 2025-06-01 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Optical mapping in Black genomes: Distinct LCR22 structures and 22q11.2 deletion syndrome mechanisms

  Genetics in Medicine · 2025-10-21 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Charting Brain Structure in 22q11.2 Deletion Syndrome with Clinical Neuroimaging

  medRxiv · 2025-11-27 · 1 citations

  preprintOpen access

  Background: 22q11.2 deletion syndrome (22q11DS) is a common microdeletion associated with widespread brain alterations and elevated risk for schizophrenia and other neuropsychiatric conditions. Prospective research studies often exclude individuals with severe cognitive impairment, medical comorbidities, or inability to tolerate research MRI without sedation, features common in 22q11DS. This limits both the generalizability of neuroimaging findings and our understanding of the full phenotypic spectrum. Moreover, while standard brain growth charts quantify deviation from typical development, they cannot identify patients who are disproportionately affected relative to their genetic peers, limiting clinical utility for risk stratification. Leveraging clinical MRI data offers a scalable approach to address these gaps. Methods: We analyzed 92 patients with 22q11DS (age 0.5-21 years, 49% female) and 252 matched clinical controls. Using normative modeling derived from 1,995 reference clinical scans, we quantified individual-level brain deviations from population norms. We validated clinical findings against the independent ENIGMA-22q research consortium, characterized rates of extreme structural deviations to assess within-syndrome heterogeneity, correlated spatial patterns of brain alterations with gene expression from the Allen Human Brain Atlas, and generated syndrome-specific growth charts to test whether deviations from syndrome-specific norms predicted cognitive and language outcomes. Results: Patients with 22q11DS showed widespread reductions in brain volumes (max Cohen's d=-1.31) and cortical surface area (d=-0.71) with increased cortical thickness (d=0.39). These findings were highly convergent with the ENIGMA-22q research cohort (r=0.61-0.87). Forty percent of patients showed at least one global brain measure below the 2.5th percentile. Spatial patterns of cortical volume and surface area correlated with the expression of genes within the 22q11.2 locus. Critically, syndrome-specific growth charts revealed that smaller cerebellar volume relative to 22q11DS peers predicted lower language scores across two independent assessment methods (p<0.03), demonstrating potential prognostic utility. Conclusions: This study provides a critical proof of principle for using heterogeneous clinical imaging to robustly characterize brain structure in rare genetic disorders. Syndrome-specific growth charts provide a novel framework to quantify within-syndrome variability and demonstrate potential prognostic value by linking individual brain structure to cognitive outcomes.

  PublisherOA PDFDOI

• Remote assessment of the Penn computerised neurocognitive battery in individuals with 22q11.2 deletion syndrome

  Journal of Intellectual Disability Research · 2024-01-16 · 3 citations

  articleOpen access

  BACKGROUND: Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in-person assessment can be unavailable or burdensome. The current study compares in-person and remote assessments of the Penn computerised neurocognitive battery (CNB). METHODS: Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in-person at a laboratory (n = 222) or remotely (n = 162). RESULTS: Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. CONCLUSIONS: These findings suggest that the CNB can be used in remote settings to assess multiple neurocognitive domains.

  PublisherOA PDFDOI

• Hearing Loss in Children with 22q11.2 Deletion Syndrome

  The Laryngoscope · 2024-09-21 · 3 citations

  article

  OBJECTIVES: Hearing loss is considered common in children with 22q11.2 deletion syndrome (22q11.2DS), with a few prior studies reporting a 32%-78% prevalence; mild-moderate conductive hearing loss has been reported most commonly. Overall, however, there remains a paucity of data regarding the frequency, type, age, and progression of hearing loss in children with 22q11.2DS. METHODS: Retrospective chart review was completed, and data combined for two large 22q centers. Inclusion criteria were children with 22q11.2DS and a documented audiogram. Data extracted included a laboratory-confirmed chromosome 22q11.2 deletion; co-morbidities; results of all audiograms and radiologic temporal bone imaging; and otologic surgical procedures. RESULTS: One thousand seven hundred sixty-nine charts were reviewed; 775 met inclusion criteria. Of these, 563 (73%) children had at least one abnormal audiogram demonstrating hearing loss. A total of 2,536 audiograms were reviewed; 74% of these showed abnormal hearing in at least one ear. Most of the hearing loss was conductive (right ear 76%; left ear 69%) and mild severity. For the children with SNHL, 90% of all follow-up audiograms were stable without progression. Hearing loss was identified across all pediatric age ranges. Ear tube placement occurred in 39% of children. CONCLUSION: This study confirms the high incidence of hearing loss for children with 22q11.2DS at some point in their childhood. In our cohort, hearing loss occurred in 73% of children and was most often conductive and mild in severity. The results highlight the importance of otolaryngology and audiology involvement in managing children with 22q11.2DS for timely diagnosis and treatment of hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 135:929-934, 2025.

  PublisherDOI

• P217: Abnormalities of TBX1 result in broad overlapping features of 22q11.2 deletion syndrome

  Genetics in Medicine Open · 2024-01-01 · 1 citations

  articleOpen access

  Tbx1 is a member of the Tbox family of binding domain transcription factors. Mice haploinsufficient for Tbx1 have features associated with 22q11.2 deletion syndrome (22q11.2DS). Tbx1-homozygous null mutant mouse embryos die at birth with cleft palate, absent thymus and parathyroid glands, truncus arteriosus and ventricular septal defects. Despite this association with structural anomalies, and more recently autism, clinicians may be unaware of the importance of considering variants in TBX1, located within the 22q11.2 DiGeorge critical region, as a potential etiology to explain findings in individuals with overlapping features of 22q11.2DS but without a deletion.

  PublisherOA PDFDOI

Recent grants

• NIH Grant M01RR000240

  NIH · $6.4M · 2006

• NIH Grant U01MH087636

  NIH · $4.6M · 2017

• Mouse functional analysis of genes for congenital heart disease

  NIH · $26.5M · 2011–2022

• NIH Grant R01CA046274

  NIH · $5.0M · 2015

• NIH Grant P50HG000425

  NIH · $11.0M · 1997

Frequent coauthors

• Elaine H. Zackai

  Children's Hospital of Philadelphia

  513 shared

• Donna M. McDonald‐McGinn

  Philadelphia University

  442 shared

• Marcia L. Budarf

  Montreal Heart Institute

  270 shared

• Raquel E. Gur

  Children's Hospital of Philadelphia

  180 shared

• Anne S. Bassett

  Centre for Addiction and Mental Health

  122 shared

• Deborah A. Driscoll

  University of Pennsylvania

  113 shared

• Bernice E. Morrow

  Albert Einstein College of Medicine

  107 shared

• Doron Gothelf

  Edmond and Lily Safra Children's Hospital

  90 shared