Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov;185(11):3485-3493.
doi: 10.1002/ajmg.a.62473. Epub 2021 Sep 3.

Expanding the phenotype: Four new cases and hope for treatment in Bachmann-Bupp syndrome

Elizabeth A VanSickle  1   2 , Julianne Michael  1   2 , André S Bachmann  2   3 , Surender Rajasekaran  1   2 , Jeremy W Prokop  3 , Ruben Kuzniecky  4 , Floris C Hofstede  5 , Katharina Steindl  6 , Anita Rauch  6 , Mark H Lipson  7 , Caleb P Bupp  1   2
Affiliations

Expanding the phenotype: Four new cases and hope for treatment in Bachmann-Bupp syndrome

Elizabeth A VanSickle et al. Am J Med Genet A. 2021 Nov.

Erratum in

Abstract

Bachmann-Bupp syndrome (BABS) is a rare syndrome caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC coded by the ODC1 gene). BABS is characterized by developmental delay, macrocephaly, macrosomia, and an unusual pattern of non-congenital alopecia. Recent diagnosis of four more BABS patients provides further characterization of the phenotype of this syndrome including late-onset seizures in the oldest reported patient at 23 years of age, representing the first report for this phenotype in BABS. Neuroimaging abnormalities continue to be an inconsistent feature of the syndrome. This may be related to the yet unknown impact of ODC/polyamine dysregulation on the developing brain in this syndrome. Variants continue to cluster, providing support to a universal biochemical mechanism related to elevated ODC protein, enzyme activity, and abnormalities in polyamine levels. Recommendations for medical management can now be suggested as well as the potential for targeted molecular or metabolic testing when encountering this unique phenotype. The natural history of this syndrome will evolve with difluoromethylornithine (DFMO) therapy and raise new questions for further study and understanding.

Keywords: Bachmann-Bupp syndrome; DFMO; ODC1; alopecia; macrocephaly; polyamines.

PubMed Disclaimer

Conflict of interest statement

André S. Bachmann, Surender Rajasekaran, and Caleb P. Bupp are listed inventors of a pending U.S. patent application based on the method of treating or preventing developmental disorders associated with mutations in the ODC1 gene. All other authors declare no conflict of interest as it relates to the content in this article.

Figures

FIGURE 1
FIGURE 1
Representative clinical phenotypes from cases 6 to 8. The first three panels show the physical facial phenotypes of the patient presented in Case 6 at ages 1, 4, and 9 years. The fourth panels demonstrate the hair loss seen from birth (top panel) to age 1 month (bottom panel) for the patient presented in Case 7, as well as the physical facial phenotype of the same patient in the fifth panels. The last panels show the physical facial phenotypes as well as hair loss of the patient presented in Case 8 at age 23 years
FIGURE 2
FIGURE 2
ODC1 gain‐of‐function variants for all nine cases thus far. (a) Exon map of the ODC1 gene, where exon 3–12 code for the ODC protein (dark green). Light green represents the untranslated regions of the gene. (b) Sequence alignment of ODC and resulting patient proteins. Conservation is shown on the top for 220 vertebrate species on a scale of 1–9 with 9 highest. Splice site of exons 11 and 12 is shown in yellow. The position of the gain‐of‐function mouse model stop codon is marked with X. (c) Protein model of the ODC dimer with exon 12 sequence marked in red
See this image and copyright information in PMC

References

    1. Alirol, E. , Schrumpf, D. , Amici Heradi, J. , Riedel, A. , de Patoul, C. , Quere, M. , & Chappuis, F. (2013). Nifurtimox‐eflornithine combination therapy for second‐stage gambiense human African trypanosomiasis: Medecins sans Frontieres experience in The Democratic Republic of the Congo. Clinical Infectious Diseases, 56, 195–203. 10.1093/cid/cis886 - DOI - PubMed
    1. Bupp, C. P. , Schultz, C. R. , Uhl, K. L. , Rajasekaran, S. , & Bachmann, A. S. (2018). Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features. American Journal of Medical Genetics Part A, 176, 2548–2553. 10.1002/ajmg.a.40523 - DOI - PubMed
    1. Casero, R. A., Jr. , & Marton, L. J. (2007). Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nature Reviews Drug Discovery, 6, 373–390. 10.1038/nrd2243 - DOI - PubMed
    1. Gerner, E. W. , & Meyskens, F. L., Jr. (2004). Polyamines and cancer: Old molecules, new understanding. Nature Reviews Cancer, 4, 781–792. 10.1038/nrc1454 - DOI - PubMed
    1. Lek, M. , Karczewski, K. J. , Minikel, E. V. , Samocha, K. E. , Banks, E. , Fennell, T. , O'Donnell‐Luria, A. H. , Ware, J. S. , Hill, A. J. , Cummings, B. B. , Tukiainen, T. , Birnbaum, D. P. , Kosmicki, J. A. , Duncan, L. E. , Estrada, K. , Zhao, F. , Zou, J. , Pierce‐Hoffman, E. , Berghout, J. , … Exome Aggregation Consortium . (2016). Analysis of protein‐coding genetic variation in 30,706 humans. Nature, 536, 285–291. 10.1038/nature19057 - DOI - PMC - PubMed

Publication types

MeSH terms