Abstract
BackgroundHeterozygous mutations of the ACAN gene are a major cause of different evolutive growth defects in the pediatric population, but were never described as a cause of fetal skeletal dysplasia.Case presentationA G1 at 21w + 3d came to our institution for the second-trimester ultrasound and a skeletal dysplasia with prevalent involvement of limb’s rhizomelic tracts was suspected. Amniocentesis followed by CGH-array was performed, with normal results. An examination by NGS of some genes associated with skeletal dysplasias showed a novel pathogenic variant of the ACAN gene: c.2677delG.ConclusionSequence variations of ACAN were never described as a possible cause of fetal skeletal anomalies to date. In this case report, we describe the first prenatal diagnosis of skeletal dysplasia associated with a pathogenic variant of ACAN.
Highlights
Heterozygous mutations of the ACAN gene are a major cause of different evolutive growth defects in the pediatric population, but were never described as a cause of fetal skeletal dysplasia.Case presentation: A G1 at 21w + 3d came to our institution for the second-trimester ultrasound and a skeletal dysplasia with prevalent involvement of limb’s rhizomelic tracts was suspected
Amniocentesis followed by CGHarray and Next Generation Sequencing (NGS) was performed and the fetus was found out to be a de novo carrier of a heterozygous pathogenic sequence variation of the ACAN gene, which codes for aggrecan
Small trials involving GH therapy after birth have been conducted in children with ACAN mutations and the therapy resulted in a possible height improvement [6]
Summary
The prenatal finding of fetal short long bones represents a challenging condition for the physician and the patient, due to its association with skeletal dysplasia, chromosomal abnormalities, and genetic syndromes [1,2,3]. Heterozygous pathogenic sequence variations of the ACAN gene (coding for the proteoglycan aggrecan) were associated with evolutive growth defects, ranging from mild idiopathic short stature to severe. The ACAN gene in a fetus with severe fetal growth restriction with prevalent reduction of the rhizomelic bones biometry. Amniocentesis was performed to exclude chromosomal, genomic, and genetic anomalies, with particular regard to some genes associated with skeletal dysplasias. Based on the clinical features associated with ACAN mutations a diagnosis of osteochondrodysplasia with short limbs and a possible future involvement of the spine and joints were done.
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