The Diagnosis and Treatment of Rare Diseases Is Our Specialty

A toddler boys sits on his mother's lap at the doctor's office. They are sitting at a table and a male doctor is sitting across from them. The mother and child are smiling at the doctor as he speaks.

Department of Pediatrics Annual Report – 2024

Clinical Genetics

2024 Pediatrics Annual Report banner

The Division of Clinical Genetics provides excellent, comprehensive care to newborns, children, and adults with known or suspected genetic disorders. Our services include: 

  • Clinical evaluation and risk assessment, genetic counseling, and comprehensive genomic testing 
  • Ongoing care and care coordination for patients with a variety of genetic conditions 
  • Identification of research studies through which patients may gain a better understanding of their conditions or access new treatments 
  • Second-opinion services to reassess previously performed genomic tests, as indicated by a review of medical records 

Division members provide genetic expertise to and collaborate with several multidisciplinary programs, including:  

  • Craniofacial Program 
  • Vascular Anomalies Program 
  • Lysosomal Storage Disorders Program 

The Division is a National Organization of Rare Diseases (NORD) Center of Excellence.  

Members of our Division provide comprehensive diagnostic services and cutting-edge treatment for infants and children with rare and undiagnosed diseases. We strive to make a diagnosis quickly and determine the most effective care or treatment for each patient.  

The Division collaborates on several ongoing and diverse precision medicine initiatives at CUIMC across the range of genetic conditions. Our research portfolio extends from basic genetic discoveries and understanding genetic mechanisms to implementation science and clinical trials of new treatments, including gene therapy. We work collaboratively with many groups around the U.S. and around the world to expand newborn screening for genetic disorders, facilitate genetic and genomic testing on scale, identify novel genes for diseases, describe the natural history of rare genetic conditions, and develop new treatments and supports for patients with rare genetic diseases.  

In 2024

The Division of Clinical Genetics will begin a new and exciting era in 2025 with the arrival of Jennifer Posey, MD, PhD, as the Division Chief of the longstanding and thriving Division in the Department of Pediatrics. Dr. Posey’s arrival truly breaks new ground as she will not only lead the Division but will also serve as the inaugural Chief Genomics Officer of the Columbia University Irving Medical Center. Under Dr. Posey’s leadership, the Division will be ideally positioned to define the future of genomic medicine within the Department of Pediatrics and to partner with the Department of Medicine to provide genomic health care across the age span.   

The Division was also fortunate to successfully recruit Stephen Kaler, MD, this past year, impressively adding to the Department’s expertise in gene therapy and clinical trials. He is an internationally renowned expert in Menkes disease, a disorder of copper transport (discovered at Columbia in 1962), and is the recent recipient of a 3-year, $4.1M extramural grant from NINDS to complete preclinical toxicology studies and launch a clinical gene therapy trial for this illness.  

New Appointments 

Major Grants 

  • Priyanka Ahimaz
    • Co-Investigator on NIH-NHGRI R01 grant (#HG012655-01) on Rare Disease Detection and Escalation Support via a Learning Health System (RESCUE) 
  • Andres Morales Corado, MD
    • Principal Investigator on A Natural History Study of Sanfilippo Syndrome Type D (MPSIIID) NIH 1UB1NS122644-01A1. NCT05648851 $370,341 
      • Goal: data collection through an observational study to determine the clinical features of patients affected by Sanfilippo syndrome type D throughout their lifetime 
  • Gustavo Maegawa, Principal Investigator  
    • Healthcare Education in Lysosomal Storage Disease Complex Care. Sanofi.  
    • An Open-Label, Multicenter, Phase 4 Study to Assess the Effects of a Prophylactic Immune Tolerizing Regimen in MPS II Treatment-Naïve Patients Planned to Receive ELAPRASE who are at Risk of Developing Persistent Neutralizing Antibodies. Takeda Pharmaceutical Co. PI: Gustavo Maegawa 
    • A Phase III study of JR-141 in Mucopolysaccharidosis type II (Hunter Syndrome) patients. JCR Pharmaceuticals. PI: Gustavo Maegawa 
    • A Phase 1, Open-label, Safety, Tolerability, and Efficacy Study of FLT201 in Adult Patients with Gaucher Disease Type 1 (GALILEO-1). Freeline Adult Patients with Gaucher Disease Type 1 (GALILEO-1). Freeline Therapeutics. PI: Gustavo Maegawa 

Selected Publications 

  • Abstracts
    • A Novel 13q31.3q32.3 Deletion Identified on Follow Up of an Inconclusive Prenatal Cell-Free DNA Screening for Trisomy 13 (P200) Sara M. Berger, Yoshiko Mito, Lakshmi Mehta. Annual meeting of the American College of Medical Genetics, Toronto, Canada. March 2024 
    • Tissue specific pathogenic NIPBL variant causing Cornelia de Lange syndrome: a call to clinicians. Lakshmi Mehta, Yakira Begun, May Sanyoura, Christine Stanley. Annual meeting of the American College of Medical Genetics, Toronto, Canada. March 2024  
  • Publications
    • Jiang N, Sewell TB, Kowalski TL, Rekab A, Hills S, Fazlollahi L, Lauren CT, Morel K, Mehta L, Liao J. Homozygous deletion of the DSG3 terminal exon associated with acantholytic blistering of the oral and laryngeal mucosa. Am J Med Genet A. 2024 Feb;194(2):389-393. doi: 10.1002/ajmg.a.63447. Epub 2023 Oct 18. PMID: 37850634. 
    • Mullegama SV, Kiernan KA, Torti E, Pavlovsky E, Tilton N, Sekula A, Gao H, Alaimo JT, Engleman K, Rush ET, Blocker K, Dipple KM, Fettig VM, Hare H, Glass I, Grange DK,  Griffin M, Phornphutkul C, Massingham L, Mehta L, Miller DE, Thies J Merritt 2nd JL, Muller E, Osmond M, Sawyer SL,
    • Slaugh R, Hickey RE,  Wolf B; Care4Rare Canada Consortium; Undiagnosed Diseases Network; Choudhary S, Simonović M, Zhang Y, Palculict TB, Telegrafi A, Carere DA, Wentzensen IM, Morrow MM, Monaghan KG, Juusola J, Yang J.
    • De novo missense variants in exon 9 of SEPHS1 cause a neurodevelopmental condition with developmental delay, poor growth, hypotonia, and dysmorphic features. American Journal of Human Genetics 2024. PMID: 38749428 DOI: 10.1016/j.ajhg.2024.05.004 
    • Schincariol-Manhe B, Campagnolo E, Spineli-Silva S, de Leeuw N, Roldão Correia-Costa G, Pessoa A, Moura de Souza CF, Stevens C, Javaher P, Fabbri Scallet H, Mohr J, Biskup S, Herkert JC, Pfundt R, Mehta L,  Rekab A, Zghal Elloumi H, Sanyoura M, Maciel-Guerra AT, Gil-da-Silva-Lopes VL, Mondadori Dos Santos A, Paiva Vieira T. Novel variants in the SOX11 gene: clinical description of seven new patients. Eur J Hum Genet . 2024 Sep 27. doi: 10.1038/s41431-024-01695-8. Online ahead of print. PMID: 39333428 
    • Karger LM, Webb BD, Edelmann L, Liao J, Mehta L.  Familial RPL26 Variant Causing Congenital Anomalies Without Hematological Features of Diamond Blackfan Anemia. Am J Med Genet A. 2024 Dec 22:e63954. doi: 10.1002/ajmg.a.63954. Online ahead of print. PMID: 39710607 
    •  Ahimaz, P., Bergner, A. L., Florido, M. E., Harkavy, N., & Bhattacharyya, S. (2024). Genetic counselors' utilization of ChatGPT in professional practice: A cross-sectional study. American journal of medical genetics. Part A, 194(4), e63493. https://doi.org/10.1002/ajmg.a.63493  
    • Cheung, C., Berger, S. M., Ross, M., Kramer, T., Li, Y., Andrews, C., Dergham, K. R., Spitz, E., Florido, M. E., & Ahimaz, P. (2024). Assessing management practices for variants of uncertain significance among genetic counselors in pediatrics. Journal of genetic counseling, 33(6), 1312–1322. https://doi.org/10.1002/jgc4.1860 
    • Freiman, A., Rekab, A., Bergner, A. L., Pereira, E. M., Lin, Y., & Ahimaz, P. (2024). Exploring the evolving roles of clinical geneticists and genetic counselors in the era of genomic medicine. American journal of medical genetics. Part A, 194(4), e63502. https://doi.org/10.1002/ajmg.a.63502  
    • Chen, F., Ahimaz, P., Nguyen, Q. M., Lewis, R., Chung, W. K., Ta, C. N., Szigety, K. M., Sheppard, S. E., Campbell, I. M., Wang, K., Weng, C., & Liu, C. (2024). Phenotype driven molecular genetic test recommendation for diagnosing pediatric rare disorders. NPJ digital medicine, 7(1), 333. https://doi.org/10.1038/s41746-024-01331-1 
    • Chan, A.K., Bogyo, K., Geltzeiler, A.R., Zhang, Y., & Ahimaz, P. (2024). Piloting an Educational Module on Consenting for Exome Sequencing Among Non-Genetics Physicians at a Medical Institution. Journal of Continuing Education in the Health Professions. 
    • Lesmana H, Kim SY, Morales Corado A, Poskanzer SA. Casgevy (exagamglogene autotemcel) and Lyfgenia (lovotibeglogene autotemcel) for individuals 12 years and older with sickle cell disease (SCD) and recurrent vaso-occlusive crises (VOC): A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG). Genet Med Open. 2024;9:101875 
    • Selvam P, Mares Beltrán CF, Sen K, Morales Corado A. Trofinetide approved for children and adults with Rett syndrome (RTT): A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG). Genet Med Open. 2024;2:101856. 
    • Corado AM. Hyperammonemia and inborn errors of metabolism. 2024 Feb 29. Trans Ped. AME Pub;13(2). Available from: https://tp.amegroups.org/issue/view/1390 
    • Dharmadhikari AV, Abad MA, Khan S, Maroofian R, Sands TT, Ullah F, Samejima I, Wear MA, Moore KE, Kondakova E, Mitina N, Schaub T, Lee GK, Umandap CH, Berger SM, Iglesias AD, Popp B, Jamra RA, Gabriel H, Rentas S, Rippert AL, Izumi K, Conlin LK, Koboldt DC, Mosher TM, Hickey SE, Albert DVF, Norwood H, Lewanda AF, Dai H, Liu P, Mitani T, Marafi D, Pehlivan D, Posey JE, Lippa N, Vena N, Heinzen EL, Goldstein DB, Mignot C, de Sainte Agathe JM, Al-Sannaa NA, Zamani M, Sadeghian S, Azizimalamiri R, Seifia T, Zaki MS, Abdel-Salam GMH, Abdel-Hamid M, Alabdi L, Alkuraya FS, Dawoud H, Lofty A, Bauer P, Zifarelli G, Afzal E, Zafar F, Efthymiou S, Gossett D, Towne MC, Yeneabat R, Wontakal SN, Aggarwal VS, Rosenfeld JA, Tarabykin V, Ohta S, Lupski JR, Houlden H, Earnshaw WC, Davis EE, Jeyaprakash AA, Liao J. RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS. medRxiv [Preprint]. 2024 Jan 9:2024.01.09.23300329. doi: 10.1101/2024.01.09.23300329. PMID: 38260255; PMCID: PMC10802637.  
    • SahBandar IN, Maegawa GHB, Brandman D, Rand JH, Lim HI, Geyer JT. A diagnosis of non-neuronopathic and late-onset acid sphingomyelinase deficiency (Niemann-Pick disease A/B) following bone marrow biopsy showing foamy histiocytosis. EJHaem. 2024 Sep 11;5(5):1078-1079. doi: 10.1002/jha2.1003. PMID: 39415905; PMCID: PMC11474401. 
    • Chang S, Zhan X, Liu Y, Song H, Gong Z, Han L, Maegawa GHB, Gu X, Zhang H. Newborn Screening for 6 Lysosomal Storage Disorders in China. JAMA Netw Open. 2024 May 1;7(5):e2410754. doi: 10.1001/jamanetworkopen.2024.10754. Erratum in: JAMA Netw Open. 2024 May 1;7(5):e2419382. doi: 10.1001/jamanetworkopen.2024.19382. PMID: 38739391; PMCID: PMC11091758. 
    • Liang H, Zhan X, Wang Y, Maegawa GHB, Zhang H. Development and validation of a new genotype-phenotype correlation for Niemann-Pick disease type C1. J Inherit Metab Dis. 2024 Mar;47(2):317-326. doi: 10.1002/jimd.12705. Epub 2023 Dec 22. PMID: 38131230. 
    • Brown RF, Close CT, Mailes MG, Gonzalez LJ, Goetz DM, Filigno SS, Preslar R, Tran QT, Hempstead SE, Lomas P, Brown AW, Flume PA; CFF Care Model Committee. Cystic fibrosis foundation position paper: Redefining the cystic fibrosis care team. J Cyst Fibros. 2024 Nov;23(6):1045-1054. doi: 10.1016/j.jcf.2024.09.011. Epub 2024 Sep 25. PMID: 39327194.