Detailed clinical and radiological features of the first patient with Elsahy-Waters syndrome in East Asia

July 20, 2021

Case Reports

doi: 10.1002/ajmg.a.62423.

Online ahead of print.

Affiliations

¹ Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
² Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.
³ Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan.
⁴ Department of Plastic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
⁵ Research Center for Supports to Advanced Science, Matsumoto, Japan.
⁶ Division of Clinical Sequencing, Matsumoto, Japan.

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Case Reports

Mari Minatogawa et al.

Am J Med Genet A.

2021.

doi: 10.1002/ajmg.a.62423.

Online ahead of print.

Affiliations

¹ Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
² Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.
³ Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan.
⁴ Department of Plastic Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
⁵ Research Center for Supports to Advanced Science, Matsumoto, Japan.
⁶ Division of Clinical Sequencing, Matsumoto, Japan.

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Abstract

Elsahy-Waters syndrome (EWS; OMIM#211380) is a rare autosomal recessive disorder that is caused by loss-of-function variants in CDH11, which encodes cadherin 11. EWS is characterized by brachycephaly, midface hypoplasia, characteristic craniofacial morphology, cervical fusion, cutaneous syndactyly in 2-3 digits, genitourinary anomalies, and intellectual disability. To the best of our knowledge, there have been only six patients of molecularly confirmed EWS. We report the first patient of EWS in East Asia in a Japanese man with a novel splice site homozygous variant of CDH11. We reviewed the clinical and molecular findings in previously reported individuals and the present patient. In addition to the previously reported clinical features of EWS, the present patient had unreported findings of atlantoaxial instability due to posterior displacement of dens, thoracic fusion, thoracic butterfly vertebra, sacralization of the lumbar vertebra (L5), and multiple perineural cysts. The spinal findings in this patient could represent a new spectrum of skeletal phenotypes of EWS. It remains to be clarified whether the multiple perineural cysts in the patient were associated with EWS or coincidental. The current observation might contribute to an expanded understanding of the clinical consequences of loss-of-function of cadherin 11.

Keywords:

CDH11; Elsahy-Waters syndrome; skeletal manifestations.

References

REFERENCES

1. Castori, M., Cascone, P., Valiante, M., Laino, L., Iannetti, G., Hennekam, R. C. M., & Grammatico, P. (2010). Elsahy-Waters syndrome: Evidence for autosomal recessive inheritance. American Journal of Medical Genetics Part A, 152A, 2810-2815. http://dx.doi.org/10.1002/ajmg.a.33634.
1. Castori, M., Ott, C. E., Bisceglia, L., Leone, M. P., Mazza, T., Castellana, S., Tomassi, J., Lanciotti, S., Mundlos, S., Hennekam, R. C., Kornak, U., & Brancati, F. (2018). A novel mutation in CDH11, encoding cadherin-11, cause Branchioskeletogenital (Elsahy-Waters) syndrome. (2018). American Journal of Medical Genetics Part A, 176, 2028-2033. https://doi.org/10.1002/ajmg.a.40379
1. El-Sahy, N. I., & Waters, W. R. (1971). The branchio-skeleto-genital syndrome. A new hereditary syndrome. Plastic and Reconstructive Surgery, 48, 542-550. https://doi.org/10.1097/00006534-197112000-00004
1. Harms, F. L., Nampoothiri, S., Anazi, S., Yesodharan, D., Alawi, M., Kutsche, K., & Alkuraya, F. S. (2018). Elsahy-Waters syndrome is caused by biallelic mutations in CDH11. American Journal of Medical Genetics Part A, 176, 477-482. https://doi.org/10.1002/ajmg.a.40379
1. Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., & Rehm, H. L. (2015). ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17, 405-424. https://doi.org/10.1038/gim.2015.30