The Diagnosis and Treatment of Rare Diseases Is Our Specialty

Mother sits with toddler on her lap while she speaks with Pediatrician.

Department of Pediatrics Annual Report – 2023

Clinical Genetics

Banner graphic for the Department of Pediatrics Annual Report for 2023

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

  • Clinical evaluation and risk assessment, genetic counseling, and comprehensive genomic testing
  • Second-opinion services reassessing previously performed genomic tests to evaluate patients with undiagnosed disorders
  • Ongoing care and care coordination for patients with genetic conditions
  • Identification of research studies through which patients may gain a better understanding of their conditions or access new treatments
  • Access to reproductive options to enable patients who are planning their families to have healthy children

Division members provide genetic expertise to and collaborate with several multidisciplinary programs at Columbia University Irving Medical Center (CUIMC), including:

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 of rare diseases and complex conditions quickly, and determine the most effective therapy for those with genetic diagnoses including clinical trials for N of 1 custom therapies, gene therapy, and RNA therapy. Through the Inherited Metabolic Disease Program, specialists focus on genetic metabolic diseases, many of which are detected through state-mandated newborn screening programs.

Research

The division collaborates on a number of 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 and N of 1 treatments with custom design antisense oligonucleotides. 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.

Education

Fellowship Program

Through our two-year program in medical genetics, fellows receive training in pediatric genetics, biochemical genetics, cytogenetics, molecular genetics, and cancer genetics, and upon graduation are capable of diagnosing and caring for patients with a wide range of genetic problems. We also have a combined pediatrics/genetics residency program in which, over the course of four years, residents are trained and board eligible for both specialties. Residents rotate through pediatric genetics, biochemical genetics, cytogenetics, molecular genetics, and cancer genetics. Fellows dedicate the remaining six months to research. Training includes intensive didactic lectures taught by faculty in the division and faculty from various departments at CUIMC. Fellows actively participate in weekly divisional conferences and present and discuss complex cases in their care.

Student, Resident, and Fellow Rotations in Clinical Genetics

Rotations in clinical genetics are available to genetic counseling students, medical students, and pediatric residents as well as trainees in other departments at CUIMC.

Learn More About Our Division

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Major Grants

  • Healthcare Education in Lysosomal Storage Disease Complex Care. Sanofi. PI: Gustavo Maegawa
  • 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 Therapeutics. PI: Gustavo Maegawa

Selected Publications

  • Jiang N, Sewell TB, Kowalski TL, Rekab A, Hills S, Fazlollahi L, Lauren CT, Morel K, Mehta L, Liao J. (2023). Homozygous deletion of the DSG3 terminal exon associated with acantholytic blistering of the oral and laryngeal mucosa. American Journal of Medical Genetics Part A,1-5. doi: 10.1002/ajmg.a.63447
  • Ahimaz P, Kramer T, Swaroop P, Mitchell M, Hernan R, Anyane-Yeboa W, Pereira EM. Assessment of the beliefs, needs, and expectations for genetic counseling of patients with hypermobile Ehlers-Dnalos syndrome. AJMG Part A. 2022 Nov;188(11):3172–3183.
  • Küry S, Zhang J, Besnard T, Caro-Llopis A, Zeng X, Robert SM, Josiah SS, Kiziltug E, Denommé-Pichon AS, Cogné B, Kundishora AJ, Hao LT, Li H, Stevenson RE, Louie R, Deb W, Torti E, Vignard V, McWalter K, Raymond FL, Rajabi F, Ranza E, Grozeva D, Coury SA, Blanc X, Brischoux-Boucher E, Keren B, Õunap K, Reinson K, Ilves P, Wentzensen IM, Barr EE, Guihard SH, Charles P, Seaby EG, Monaghan KG, Rio M, van Bever Y, van Slegtenhorst M, Chung WK, Wilson A, Quinquis D, Bréhéret F, Retterer K, Lindenbaum P, Scalais E, Rhodes L, Stouffs K, Pereira EM, Berger SM, Milla SS, Jaykumar A, Cobb M, Panchagnula S, Duy PQ, Vincent M, Mercier S, Gilbert-Dussardier B, Audebert-Bellanger S, Odent S, Schmitt S, Boisseau P, Bonneau D, Toutain A, Colin E, Pasquier L, Redon R, Bouman A, Rosenfeld JA, Friez MJ, Pena HP, Rizvi SRA, Haider S, Antonarakis SE, Schwartz CE, Martínez F, Bézieau S, Kahle KT, Isidor B. Rare, pathogenic variants in WNK3 cause X-linked intellectual disability. Genet Med. 2022 Sept 24(9):1941-1951.
  • Pereira, EM. In Brief: Gene Therapy Update. Pediatrics in Review. 2022 Sept;43(9):536-537
  • Dharmadhikari AV, Pereira EM, Andrews CC, Macera M, Harkavy N, Wapner R, Jobanputra V, Levy B, Ganapathi M, Liao J. Case Report: Prenatal Identification of a De Novo Mosaic Neocentric Marker Resulting in 13q31.1→qter Tetrasomy in a Mildly Affected Girl. 2022, Front Genet. Jul 19;13: 906077.
  • Barua S, Berger S, Pereira EM, Jobanputra V. Expanding the phenotype of ATPGAP1 deficiency. Cold Spring Harb Mol Case Stud. 2022, June 8(4), a006195.
  • Corado AM. Hyperphenylalaninemia, BH4 deficient (HPABH4). 2023 Feb 12. In: Rezaei, N (eds) Genetic syndromes. Springer Cham. https://doi.org/10.1007/978-3-319-66816-1_1759-1
  • Martino J, Liu Q, Vukojevic K, Ke J, Lim TY, Khan A, Gupta Y, Perez A, Yan Z, Milo Rasouly H, Vena N, Lippa N, Giordano JL, Saraga M, Saraga-Babic M, Westland R, Bodria M, Piaggio G, Bendapudi PK, Iglesias AD, Wapner RJ, Tasic V, Wang F, Ionita-Laza I, Ghiggeri GM, Kiryluk K, Sampogna RV, Mendelsohn CL, D'Agati VD, Gharavi AG, Sanna-Cherchi S. Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies. Genet Med. 2023 Dec;25(12):100983. doi: 10.1016/j.gim.2023.100983.
  • Wilkins SR, Yu AW, Steigerwald C, Tanji K, Iglesias AD, Hirano M, Kister I, Riley CS, Abreu NJ.
  • Mult Scler. Two cases of MT-ND5-related mitochondrial disorder misdiagnosed as seronegative neuromyelitis optica spectrum disorder. 2023 Jun;29(7):892-897. doi: 10.1177/13524585231172947.
  • Lotan D, DeFilippis EM, Oren D, Vinogradsky A, Rubinstein G, Mathur A, Takeda K, Hua M, Gaglio PJ, Szabolcs MJ, Sayer G, Uriel N, Iglesias AD, Latif F. Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia. Nutr Metab Cardiovasc Dis. 2023 Mar;33(3):667-670. doi: 10.1016/j.numecd.2022.12.022.
  • Ganapathi M, Matsuoka LS, March M, Li D, Brokamp E, Benito-Sanz S, White SM, Lachlan K, Ahimaz P, Sewda A, Bastarache L, Thomas-Wilson A, Stoler JM, Bramswig NC, Baptista J, Stals K, Demurger F, Cogne B, Isidor B, Bedeschi MF, Peron A, Amiel J, Zackai E, Schacht JP, Iglesias AD, Morton J, Schmetz A; Undiagnosed Diseases Network; Seidel V, Lucia S, Baskin SM, Thiffault I, Cogan JD, Gordon CT, Chung WK, Bowdin S, Bhoj E. Heterozygous rare variants in NR2F2 cause a recognizable multiple congenital anomaly syndrome with developmental delays. Eur J Hum Genet. 2023 Oct;31(10):1117-1124. doi: 10.1038/s41431-023-01434-5.
  • Kumble S, Levy AM, Punetha J, Gao H, Ah Mew N, Anyane-Yeboa K, Benke PJ, Berger SM, Bjerglund L, Campos-Xavier B, Ciliberto M, Cohen JS, Comi AM, Curry C, Damaj L, Denommé-Pichon AS, Emrick L, Faivre L, Fasano MB, Fiévet A, Finkel RS, García-Miñaúr S, Gerard A, Gomez-Puertas P, Guillen Sacoto MJ, Hoffman TL, Howard L, Iglesias AD, Izumi K, Larson A, Leiber A, Lozano R, Marcos-Alcalde I, Mintz CS, Mullegama SV, Møller RS, Odent S, Oppermann H, Ostergaard E, Pacio-Míguez M, Palomares-Bralo M, Parikh S, Paulson AM, Platzer K, Posey JE, Potocki L, Revah-Politi A, Rio M, Ritter AL, Robinson S, Rosenfeld JA, Santos-Simarro F, Sousa SB; Undiagnosed Diseases Network; Wéber M, Xie Y, Chung WK, Brown NJ, Tümer Z. The clinical and molecular spectrum of QRICH1 associated neurodevelopmental disorder. Hum Mutat. 2022 Feb;43(2):266-282. doi: 10.1002/humu.24308

Highlights

Can Genomic Screening of Newborns Help More Children Born with Rare Diseases?

In the GUARDIAN study, the genomes of newborns are being scanned to identify children who have one of hundreds of treatable and preventable rare genetic conditions before symptoms emerge.

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