TY - JOUR

T1 - A new case of Greenberg dysplasia and literature review suggest that Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley–Kendall dysplasia are allelic disorders

AU - Gregersen, Pernille A.

AU - McKay, Victoria

AU - Walsh, Maie

AU - Brown, Erica

AU - McGillivray, George

AU - Savarirayan, Ravi

PY - 2020/6

Y1 - 2020/6

N2 - Background: Greenberg dysplasia is a rare, autosomal recessive, prenatal lethal bone dysplasia caused by biallelic pathogenic variants in the lamin B receptor (LBR) gene. Pathogenic variants in LBR are also associated with Pelger–Huët anomaly, an autosomal dominant benign abnormality of the nuclear shape and chromatin organization of blood granulocytes, and Pelger–Huët anomaly with variable skeletal anomalies, a mild, regressing to moderate–severe autosomal recessive condition. Conditions with abnormal sterol metabolism and different genetic basis have clinical and radiographic features similar to Greenberg dysplasia, for example X-linked dominant chondrodysplasia punctata, Conradi–Hünermann type, and CHILD syndrome, and other conditions with unknown genetic etiology display very similar features, for example, dappled diaphyseal dysplasia and Astley–Kendall dysplasia. Methods: We present a fetus with typical clinical and radiographic features of Greenberg dysplasia, and review the literature. Results: Genetic testing confirmed the diagnosis Greenberg dysplasia: homozygosity for a pathogenic variant in LBR. Conclusion: Comparing the clinical and radiographic phenotypes of Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley–Kendall dysplasia, we suggest that these are allelic disorders.

AB - Background: Greenberg dysplasia is a rare, autosomal recessive, prenatal lethal bone dysplasia caused by biallelic pathogenic variants in the lamin B receptor (LBR) gene. Pathogenic variants in LBR are also associated with Pelger–Huët anomaly, an autosomal dominant benign abnormality of the nuclear shape and chromatin organization of blood granulocytes, and Pelger–Huët anomaly with variable skeletal anomalies, a mild, regressing to moderate–severe autosomal recessive condition. Conditions with abnormal sterol metabolism and different genetic basis have clinical and radiographic features similar to Greenberg dysplasia, for example X-linked dominant chondrodysplasia punctata, Conradi–Hünermann type, and CHILD syndrome, and other conditions with unknown genetic etiology display very similar features, for example, dappled diaphyseal dysplasia and Astley–Kendall dysplasia. Methods: We present a fetus with typical clinical and radiographic features of Greenberg dysplasia, and review the literature. Results: Genetic testing confirmed the diagnosis Greenberg dysplasia: homozygosity for a pathogenic variant in LBR. Conclusion: Comparing the clinical and radiographic phenotypes of Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley–Kendall dysplasia, we suggest that these are allelic disorders.

KW - abnormal sterol metabolism

KW - Greenberg dysplasia

KW - LBR

KW - Skeletal dysplasia

UR - http://www.scopus.com/inward/record.url?scp=85083573223&partnerID=8YFLogxK

U2 - 10.1002/mgg3.1173

DO - 10.1002/mgg3.1173

M3 - Journal article

C2 - 32304187

AN - SCOPUS:85083573223

VL - 8

JO - Molecular Genetics & Genomic Medicine

JF - Molecular Genetics & Genomic Medicine

SN - 2324-9269

IS - 6

M1 - e1173

ER -