Clinical consequences in truncating mutations in exon 34 of NOTCH2: Report of six patients with Hajdu-Cheney syndrome and a patient with serpentine fibula polycystic kidney syndrome

Yoko Narumi, Byung Joo Min, Kenji Shimizu, Itsuro Kazukawa, Kiyoko Sameshima, Koichi Nakamura, Tomoki Kosho, Yumie Rhee, Yoon Sok Chung, Ok Hwa Kim, Yoshimitsu Fukushima, Woong Yang Park, Gen Nishimura

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Abstract

It is debatable whether Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) represent a single clinical entity with a variable degree of expression or two different entities, because both disorders share common clinical and radiological manifestations, including similar craniofacial characteristics, and defective bone mineralization. Since it was shown that heterozygous truncating mutations in NOTCH2 are responsible for both HCS and SFPKS, 37 patients with HCS and four patients with SFPKS are reported. To elucidate the clinical consequences of NOTCH2 mutations, we present detailed clinical information for seven patients with truncating mutations in exon 34 of NOTCH2, six with HCS and one with SFPKS. In addition, we review all the reported patients whose clinical manifestations are available. We found 13 manifestations including craniofacial features, acroosteolysis, Wormian bones, and osteoporosis in >75% of NOTCH2-positive patients. Acroosteolysis was observed in two patients with SFPKS and bowing fibulae were found in two patients with HCS. These clinical and molecular data would support the notion that HCS and SFPKS are a single disorder.

Original languageEnglish
Pages (from-to)518-526
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number3
DOIs
Publication statusPublished - 2013 Mar 1

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Narumi, Y., Min, B. J., Shimizu, K., Kazukawa, I., Sameshima, K., Nakamura, K., Kosho, T., Rhee, Y., Chung, Y. S., Kim, O. H., Fukushima, Y., Park, W. Y., & Nishimura, G. (2013). Clinical consequences in truncating mutations in exon 34 of NOTCH2: Report of six patients with Hajdu-Cheney syndrome and a patient with serpentine fibula polycystic kidney syndrome. American Journal of Medical Genetics, Part A, 161(3), 518-526. https://doi.org/10.1002/ajmg.a.35772