ESPE Abstracts

Introduction: Short stature is a frequent reason for consultation in the paediatric age group. After appropriate clinical, radiological and laboratory evaluation, up to 60-80% of children are classified as idiopathic short stature (ISS) because no underlying cause can be found. Nowadays, the spreading of molecular is revealing that many of the patients initially classified as TBI, have variants in genes involved in the growth plate development. IHH gene is involved in endochondral ossification of the growth plate by promoting proliferation and differentiation of the chondrocyte. Variants in this gene have been identified as a cause of short stature and minor skeletal disorders. Homozygous variants result in skeletal dysplasia known as Acrocapitofemoral Dysplasia causing extreme disproportionate short stature and cone-shaped epiphyses while heterozygous variants cause A1 Brachydactyly, characterized by short stature and shortening of the middle phalanges. We present the case of a patient with a deletion in the IHH gene classified as likely pathogenic variant and previously only described in a single patient in the literature.

Clinical report: A 12-year-old girl followed in our Paediatric Endocrinology clinic since she was 11, due to decreased growth velocity. Her anthropometry at birth was normal and the remaining personal history had no relevant findings. She had a family history of short stature especially at the maternal branch, and the mother has a heigh at -2.75 SDS. The patient’s height was at p4 at examination with adequate arm-span and sitting height/standing height ratio. She had short fingers and bilateral preauricular appendices Peripheral blood karyotype and the first level survey for growth study found no alterations. Given the familial short stature and brachydactyly history, it was decided to perform a skeletal dysplasia panel. This panel detected a heterozygous variant in the IHH gene (c.568_570del) classified as likely pathogenic variant and previously described in another patient, which would explain our patient’s phenotype.

Conclusion: The study of a patient with short stature or decreased height velocity deserves a careful physical examination for minor skeletal alterations. When these are present, and especially with a positive family history, molecular genetic testing is an unvaluable tool.