Author(s) :

Will Teitelbaum.

Volume/Issue :

Abstract :

One of the most common genetic causes of short stature is the haploinsufficiency of the Short-stature Homeobox (SHOX) gene. In this group of SHOX-related disorders, SHOX deficiency is one of the most severe forms, resulting from the loss of function of one SHOX allele. This literature review discusses the current knowledge of SHOX deficiency, including its manifestation, diagnosis, major symptoms, and treatments. It is estimated that SHOX deficiency is responsible for about 6.8% of individuals with short stature-related diseases. The use of Recombinant Human Growth Hormones (rhGH) to alleviate growth impairment has been proven effective in treating prepubertal patients who begin therapy at a young age. An Italian study on adolescents with SHOX deficiency discovered that rhGH therapy yielded an overall height gain of +0.80 ±0.98 standard deviation score (SDS) from the start of treatment to the attainment of final height, with a duration of 5.94 ± 2.00 years. However, the often mild and complex symptoms in prepubertal patients make early diagnosis challenging, and treatment occurring after the onset of puberty can limit the positive growth effects of this therapy. This review also analyzes alternative treatment options to rhGH therapy, including the use of Gonadotropin-releasing hormone agonists (GnRHa) as a way to slow down puberty progression. However, studies on the effectiveness of GnRHa remain inconclusive. Lastly, this review evaluates the potential role of the emerging CRISPR Cas9 gene-editing technology, and emphasizes the importance of and need for continued research into new methods for early diagnosis.