Expanding the phenotype of Bruck syndrome: Severe limb deformity, arthrogryposis, congenital cardiac disease and pulmonary hemorrhage

Jessica L Sandy; Darazel Perez; Shuxiang Goh; Jonathan Forsey; Sulekha Rajagopalan; Amit Trivedi; Craig F Munns

doi:10.1002/ajmg.a.63007

Expanding the phenotype of Bruck syndrome: Severe limb deformity, arthrogryposis, congenital cardiac disease and pulmonary hemorrhage

Am J Med Genet A. 2023 Jan;191(1):265-270. doi: 10.1002/ajmg.a.63007. Epub 2022 Oct 25.

Authors

Jessica L Sandy^{1

2}, Darazel Perez³, Shuxiang Goh^{2

4}, Jonathan Forsey⁵, Sulekha Rajagopalan⁶, Amit Trivedi^{3

7}, Craig F Munns^{8

9

10}

Affiliations

¹ Department of Endocrinology, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
² School of Women's and Children, University of New South Wales, Sydney, New South Wales, Australia.
³ Grace Centre for Newborn Care, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁴ Sydney Children's Hospital, Westmead, New South Wales, Australia.
⁵ Heart Centre for Children, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁶ Department of Clinical Genetics, Liverpool Hospital, Liverpool, New South Wales, Australia.
⁷ The University of Sydney, Children's Hospital Westmead clinical School, Queensland, New South Wales, Australia.
⁸ Department of Endocrinology and Diabetes, Queensland Children's Hospital, Brisbane, Queensland, Australia.
⁹ Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
¹⁰ Child Health Research Centre and Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

PMID: 36282022
DOI: 10.1002/ajmg.a.63007

Abstract

Bruck syndrome is a rare collagen disorder with autosomal recessive inheritance caused by pathogenic variants in either FKBP10 or PLOD2 genes. It is characterized by bone fragility and fractures similar in severity and variability to osteogenesis-imperfecta as well as congenital joint contractures. This article describes an infant with a homozygous (partial) gene deletion of PLOD2 that includes the start codon and would be expected to lead to nonfunctional protein product. The infant had a severe phenotype of Bruck syndrome and is the only reported case of Bruck syndrome with congenital cardiac disease (triscuspid valve dysplasia with severe regurgitation, mitral valve prolapses with moderate regurgitation, and pulmonary hypertension) and pulmonary hemorrhage. We hypothesize that the additional feature of congenital cardiac disease in this case was due to the underlying defect in type I collagen, and that the pulmonary hemorrhage was multifactorial, with underlying vessel fragility, rib fractures, and high pulmonary pressures likely to be major contributing factors. Management was largely supportive with the use of bisphosphonates to assist in pain management. Care was complicated by comorbid cardiopulmonary compromise, limited evidence-base guiding care, and difficulties in discussing end-of-life care.

Keywords: Bruck syndrome; arthrogryposis; severe limb deformity.

Publication types

Case Reports

MeSH terms

Arthrogryposis* / complications
Arthrogryposis* / diagnosis
Arthrogryposis* / genetics
Heart Defects, Congenital* / complications
Heart Defects, Congenital* / diagnosis
Heart Defects, Congenital* / genetics
Hemorrhage / diagnosis
Hemorrhage / genetics
Humans
Osteogenesis Imperfecta* / complications
Osteogenesis Imperfecta* / diagnosis
Osteogenesis Imperfecta* / genetics
Phenotype