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Am J Med Genet A. 2019 Sep;179(9):1884-1894. doi: 10.1002/ajmg.a.61282. Epub 2019 Jul 16.

PAPSS2-related brachyolmia: Clinical and radiological phenotype in 18 new cases.

Author information

1
Clinical Genetics, St Michael's Hospital Bristol, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
2
East Midlands and East of England NHS Genomic Laboratory Hub, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
3
East Anglian Medical Genetics Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
4
Département of Genetics, INSERM UMR1163, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, AP-HP, Hôpital Necker Enfants Malades, Paris, France.
5
Department of Radiology, Stavanger University Hospital, Stavanger, Norway.
6
Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
7
Department of Paediatric Endocrinology and Diabetes, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
8
Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
9
Wessex Clinical Genetics, Princess Anne Hospital, Southampton, UK.
10
Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway.
11
Department of Clinical Science, University of Bergen, Bergen, Norway.
12
Department of Paediatrics, Haukeland University Hospital, Bergen, Norway.
13
Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands.
14
Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
15
Department of Radiology, Oslo University Hospital, Oslo, Norway.
16
Department of Paediatric Orthopaedics, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
17
University of Sheffield, Academic Unit of Child Health, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
18
Section of Paediatric Radiology, Haukeland University Hospital, Bergen, Norway.
19
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
20
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
21
Department of Medical Genetics, Telemark Hospital Trust, Skien, Norway.
22
Nuffield Orthopaedic Centre, Oxford, UK.
23
Wellcome Sanger Institute, Cambridge, UK.

Abstract

Brachyolmia is a skeletal dysplasia characterized by short spine-short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short-spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over-faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi-parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under-recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester.

KEYWORDS:

PAPSS2; brachyolmia; platyspondyly

PMID:
31313512
DOI:
10.1002/ajmg.a.61282

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