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

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 simi...

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Published in:American journal of medical genetics. Part A 2013-03, Vol.161A (3), p.518-526
Main Authors: Narumi, Yoko, Min, Byung-Joo, Shimizu, Kenji, Kazukawa, Itsuro, Sameshima, Kiyoko, Nakamura, Koichi, Kosho, Tomoki, Rhee, Yumie, Chung, Yoon-Sok, Kim, Ok-Hwa, Fukushima, Yoshimitsu, Park, Woong-Yang, Nishimura, Gen
Format: Article
Language:English
Subjects:
Adolescent
Adult
Bone
Child, Preschool
Codon, Nonsense
DNA Mutational Analysis
Exons
Genetic Association Studies
Hajdu-Cheney syndrome
Hajdu-Cheney Syndrome - diagnostic imaging
Hajdu-Cheney Syndrome - genetics
Humans
Middle Aged
NOTCH2
osteolysis
osteoporosis
Radiography
Receptor, Notch2 - genetics
serpentine fibula-polycystic kidney syndrome
Young Adult
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Summary: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. © 2013 Wiley Periodicals, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.35772