Download PDF
CC BY-NC-ND 4.0 · Journal of Fetal Medicine
DOI: 10.1055/s-0045-1808250
Case Report

Fetal Exome Sequencing in Diagnosing Chondrodysplasia Punctata Associated with Maternal Systemic Lupus Erythematosus: A Case Report

Christina J. Miller    *
1   Genetic Counseling Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
,
Kestutis Micke
2   Colorado Fetal Care Center, Children's Hospital Colorado, Aurora, Colorado, United States
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Chondrodysplasia punctata (CDP) is a rare congenital disorder characterized by midface hypoplasia, stippled epiphyses, and limb shortening. Among the heterogeneous factors that cause CDP, maternal autoimmune conditions have caused 34 cases, including ours, to date. We describe a previously unreported case of CDP associated with maternal systemic lupus erythematosus (SLE). A 27-year-old G1P0 patient with a known history of SLE with anti-Ro/SSA autoantibodies was evaluated at our center at 21w1d. After reviewing fetal imaging and negative karyotype, microarray, and exome sequencing, our clinical team agreed upon establishing a clinical diagnosis of maternal SLE-associated CDP at 21 weeks' gestation. The combination of negative exome sequencing, karyotype, and chromosomal microarray analysis and relevant clinical findings enabled us to make the appropriate diagnosis at 21 weeks rather than in the third trimester or postnatally when additional phenotypic features became apparent. This earlier diagnosis provided the clinical team with time to assess additional recommended management and referrals and perhaps more importantly, provided the patient with additional time to consider her pregnancy options.

Keywords

fetal chondrodysplasia punctata - maternal SLE - systemic lupus erythematosus - exome sequencing - genetic testing - prenatal imaging

Poster Presentations

Miller, C. & Micke, K (May 19, 2023). Utility of negative fetal exome sequencing in diagnosing chondrodysplasia punctata associated with maternal systemic lupus erythematosus: a case report. Poster presentation at Colorado Clinical and Translational Sciences Institute (CCTSI) Annual Spring Pediatric Research Poster Session, Aurora, CO.

Miller, C. & Micke, K (March 16, 2023). Utility of negative fetal exome sequencing in diagnosing chondrodysplasia punctata associated with maternal systemic lupus erythematosus: a case report. Poster presentation at the Annual Conference of the American College of Medical Genetics, Salt Lake City, UT.


Statement of Conforming to Declaration of Helsinki

The work was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the participant. The privacy rights of the participant were respected. Patient data and imaging were not published without written permission.


Authors' Contributions

C.M.: conceptualization, data curation, project administration, visualization, writing – original draft, and writing – review and editing.

K.M.: conceptualization, data curation, project administration, resources, supervision, and writing – review and editing.


* Author's present address Center for Fetal Medicine and Reproductive Genetics, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, United States




Publication History

Article published online:
25 April 2025

© 2025. Society of Fetal Medicine. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Chitayat D, Keating S, Zand DJ. et al. Chondrodysplasia punctata associated with maternal autoimmune diseases: expanding the spectrum from systemic lupus erythematosus (SLE) to mixed connective tissue disease (MCTD) and scleroderma report of eight cases. Am J Med Genet A 2008; 146A (23) 3038-3053
    PubMedSearch in Google Scholar
  • 2 Elayedatt RA, Krishnan V. Rare association of fetal chondrodysplasia punctata in maternal SLE: a case report. J Foetal Med 2021; (08) 147-150
    Search in Google Scholar
  • 3 Pop LG, Suciu ID, Bacalbasa N, Toader OD. Prenatal diagnosis of Binder phenotype, naso-maxillar hypoplasia. Acta Marisiensis Ser Med 2020; 66 (04) 160-164
    Search in Google Scholar
  • 4 Tim-aroon T, Jaovisidha S, Wattanasirichaigoon D. A new case of maternal lupus-associated chondrodysplasia punctata with extensive spinal anomalies. Am J Med Genet A 2011; 155A (06) 1487-1491
    PubMedSearch in Google Scholar
  • 5 Irving MD, Chitty LS, Mansour S, Hall CM. Chondrodysplasia punctata: a clinical diagnostic and radiological review. Clin Dysmorphol 2008; 17 (04) 229-241
    PubMedSearch in Google Scholar
  • 6 Elçioglu N, Hall CM. Maternal systemic lupus erythematosus and chondrodysplasia punctata in two sibs: phenocopy or coincidence?. J Med Genet 1998; 35 (08) 690-694
    PubMedSearch in Google Scholar
  • 7 Kelly TE, Alford BA, Greer KM. Chondrodysplasia punctata stemming from maternal lupus erythematosus. Am J Med Genet 1999; 83 (05) 397-401
    PubMedSearch in Google Scholar
  • 8 Kozlowski K, Basel D, Beighton P. Chondrodysplasia punctata in siblings and maternal lupus erythematosus. Clin Genet 2004; 66 (06) 545-549
    PubMedSearch in Google Scholar
  • 9 Shanske AL, Bernstein L, Herzog R. Chondrodysplasia punctata and maternal autoimmune disease: a new case and review of the literature. Pediatrics 2007; 120 (02) e436-e441
    PubMedSearch in Google Scholar
  • 10 Roy A, De P, Chakraborty S. Rhizomelic chondrodysplasia punctata with maternal systemic lupus erythromatosus. Indian Pediatr 2013; 50 (06) 605-607
    PubMedSearch in Google Scholar
  • 11 Alkhunaizi E, Unger S, Shannon P, Nishimura G, Blaser S, Chitayat D. Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants. Am J Med Genet A 2020; 182 (07) 1807-1811
    PubMedSearch in Google Scholar
  • 12 Authreya AJ, Rajgopal D, Makam A. Fetal flat-facies on prenatal ultrasound: is it chondrodysplasia punctata? A retrospective chart review of 62 fetuses. J Foetal Med 2021; 8 (02) 147-150
    Search in Google Scholar
  • 13 Mansour S, Liberman D, Young I. Brachytelephalangic chondrodysplasia punctata in an extremely premature infant. Am J Med Genet 1994; 53 (01) 81-82
    PubMedSearch in Google Scholar
  • 14 Schulz SW, Bober M, Johnson C, Braverman N, Jimenez SA. Maternal mixed connective tissue disease and offspring with chondrodysplasia punctata. Semin Arthritis Rheum 2010; 39 (05) 410-416
    PubMedSearch in Google Scholar
  • 15 Milliken M, Lee J, Cipriano SD. Chondrodysplasia punctata and neonatal lupus in an infant with positive anti-RNP and negative anti-Ro/SSA and -La/SSB antibodies, a case report. Pediatr Dermatol 2020; 37 (05) 925-928
    PubMedSearch in Google Scholar
  • 16 Nayak SS, Adiga PK, Rai L, Girisha KM. Severe rhizomelic chondrodysplasia punctata in a fetus due to maternal mixed connective tissue disorder. Genet Couns 2012; 23 (04) 487-491
    PubMedSearch in Google Scholar
  • 17 Pandita A, Panghal A, Gupta G, Singh V. Neonatal punctate calcifications associated with maternal mixed connective tissue disorder (MCTD). BMJ Case Rep 2018; 2018: bcr2017223373
    CrossrefPubMedSearch in Google Scholar
  • 18 Huarte NM, Santos-Simarro F, Abascal IP, García-Miñaur S, Omeñaca F. Chondrodysplasia punctata associated with maternal Sjögren syndrome. Am J Med Genet A 2014; 164A (06) 1606-1610
    PubMedSearch in Google Scholar
  • 19 Vengetesh PM, Hebbar S, Rai L. Autoimmune diseases in pregnancy: maternal and fetal outcomes. Report. Int J Reprod Contracept Obstet Gynecol 2015; 4 (01) 9-14
    Search in Google Scholar
  • 20 Lim K, Pugash D, Friedman JM, Ensworth S, Dahlgren L, Kent N. OC17.04: Just images: Four consecutive pregnancies affected by chondrodysplasia punctata in a woman with mixed connective tissue disease. Ultrasound Obstet Gynecol 2005; 26 (04) 337-337
    Search in Google Scholar
  • 21 Mathe M, Delrue M, Moramarco V, Rypens F, Wavrant S. EP07.03: a case of chondrodyplasia punctata in a lupic mother. Ultrasound Obstet Gynecol 2017; 50 (S1): 290-290
    Search in Google Scholar
  • 22 Nino M, Matos-Miranda C, Maeda M. et al. Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata. Am J Med Genet A 2008; 146A (08) 997-1008
    PubMedSearch in Google Scholar
  • 23 Derdulska JM, Rudnicka L, Szykut-Badaczewska A. et al. Neonatal lupus erythematosus - practical guidelines. J Perinat Med 2021; 49 (05) 529-538
    PubMedSearch in Google Scholar
  • 24 Gryka-Marton M, Szukiewicz D, Teliga-Czajkowska J, Olesinska M. An overview of neonatal lupus with anti-Ro characteristics. Int J Mol Sci 2021; 22 (17) 9281
    PubMedSearch in Google Scholar
  • 25 Alrukban H, Chitayat D. Fetal chondrodysplasia punctata associated with maternal autoimmune diseases: a review. Appl Clin Genet 2018; 11: 31-44
    PubMedSearch in Google Scholar
  • 26 Colin E, Touraine R, Levaillant JM. et al. Binder phenotype in mothers affected with autoimmune disorders. J Matern Fetal Neonatal Med 2012; 25 (08) 1413-1418
    PubMedSearch in Google Scholar