Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant

TY - JOUR

T1 - Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant

AU - Seiersen, Kasper V

AU - Henriksen, Tine B

AU - Andelius, Ted C K

AU - Andreasen, Lotte

AU - Diemer, Tue

AU - Gudmundsdottir, Gudrun

AU - Vogel, Ida

AU - Gjørup, Vibike

AU - Gregersen, Pernille A

PY - 2024/2

Y1 - 2024/2

N2 - Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene (FGFR3). Short stature homeobox (SHOX) deficiency is caused by loss or defects of the SHOX gene or its enhancer region. It is associated with a spectrum of phenotypes ranging from normal stature to Léri-Weill dyschondrosteosis characterized by mesomelia and short stature or the more severe Langer mesomelic dysplasia in case of biallelic SHOX deficiency. Little is known about the interactions and phenotypic consequences of achondroplasia in combination with SHOX deficiency, as the literature on this subject is scarce, and no genetically confirmed clinical reports exist. We present the clinical findings in an infant girl with concurrent achondroplasia and SHOX deficiency. We conclude that the clinical findings in infancy are phenotypically compatible with achondroplasia, with no features of the SHOX deficiency evident. This may change over time, as some features of SHOX deficiency only become evident later in life.

AB - Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene (FGFR3). Short stature homeobox (SHOX) deficiency is caused by loss or defects of the SHOX gene or its enhancer region. It is associated with a spectrum of phenotypes ranging from normal stature to Léri-Weill dyschondrosteosis characterized by mesomelia and short stature or the more severe Langer mesomelic dysplasia in case of biallelic SHOX deficiency. Little is known about the interactions and phenotypic consequences of achondroplasia in combination with SHOX deficiency, as the literature on this subject is scarce, and no genetically confirmed clinical reports exist. We present the clinical findings in an infant girl with concurrent achondroplasia and SHOX deficiency. We conclude that the clinical findings in infancy are phenotypically compatible with achondroplasia, with no features of the SHOX deficiency evident. This may change over time, as some features of SHOX deficiency only become evident later in life.

KW - Achondroplasia

KW - FGFR3

KW - Infant

KW - SHOX

KW - Short stature homeobox protein

KW - Growth Disorders/genetics

KW - Humans

KW - Osteochondrodysplasias/genetics

KW - Achondroplasia/genetics

KW - Gene Deletion

KW - Homeodomain Proteins/genetics

KW - Denmark

KW - Female

KW - Short Stature Homeobox Protein/genetics

KW - Genes, Homeobox

UR - http://www.scopus.com/inward/record.url?scp=85179931911&partnerID=8YFLogxK

U2 - 10.1016/j.ejmg.2023.104894

DO - 10.1016/j.ejmg.2023.104894

M3 - Journal article

C2 - 38070826

SN - 1769-7212

VL - 67

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

M1 - 104894

ER -