ESPE Abstracts

Spondylo-epimetaphyseal dysplasia -ACAN (SEMD- ACAN) is a rare form of osteo-chondrodysplasia that represents a group of vertebral, epiphyseal, and metaphyseal dysplasia. This genetic condition is caused by biallelic loss-of-function mutations in the ACAN gene, which encodes for aggrecan, an essential component of the extracellular matrix in cartilage. Biallelic loss-of-function mutations in this gene result in a range of characteristic symptoms, including disproportionate short stature, rough facial features, midface hypoplasia, macrocephaly, thoracic deformity, mesomelia, and brachydactyly. In this case report, we present the fourth report of SEMD-ACAN in two siblings. The proband, a 9-year-old girl, presented with severe growth retardation. She was born at term with a normal weight (1.84 SDS) but severe short stature (41 cm; -3.54 SDS) to healthy consanguineous Turkish parents. Her mother had severe (-2.74 SDS) and her father had moderate (-2.3 SDS) short stature. On physical examination, the proband's weight was -1.25 SDS, height was -4.6 SDS, and she was prepubertal. She had midface hypoplasia, low-set ears, a short neck, short limbs, and truncal obesity. Biochemical and hormonal tests were all normal. In skeletal survey; moderate platyspondily, thoracolomber scoliosis, and lumbar lordosis, and bilateral femoro-acetabular narrowing were noted. The proband had disproportionate short stature with advanced bone age (10 years). In genetic analyses, we detected a homozygous ACAN variation (c.512C>T; p. Ala171Val) with next-generation sequencing (NGS). Segregation analysis revealed that the parents were both heterozygous and the proband's male sibling with a similar clinical presentation was homozygous for this variant. In literature, heterozygous form of this variant was reported in 15 year-old boy with severe short stature with advance bone age, and dysmorphic features (mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck). SEMD-ACAN is a rare genetic condition that affects bone growth and development and can result in a variety of physical and developmental abnormalities. Diagnosis of SEMD-ACAN is typically made through clinical evaluation and genetic testing. Skeletal radiography, bone age assessment, and biochemical tests may also be used to support the diagnosis. Management typically involves addressing symptoms such as short stature and skeletal abnormalities. This case report highlights the importance of considering genetic testing in cases of severe growth retardation and other characteristic symptoms associated with SEMD-ACAN.