Case Report: Sequential treatment of growth hormone deficiency and central precocious puberty in a girl with EP300-mutated Rubinstein-Taybi syndrome.

BACKGROUND

Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder defined by intellectual disability, short stature, broad thumbs and halluces, and distinct craniofacial features. The genetic etiology of RTS is primarily attributed to point mutations or deletions in the CREB-binding protein gene (CREBBP) or the E1A-binding protein gene (EP300). Endocrine abnormalities in RTS remain underreported.

CASE PRESENTATION: A 7-year-9-month-old girl with characteristic facial features of RTS presented with growth retardation [height -2.09 standard deviation score (SDS)] and premature thelarche. Genetic and endocrinological assessments confirmed EP300-mutated RTS complicated by growth hormone deficiency (GHD) and central precocious puberty (CPP). Sequential therapy was initiated: recombinant human growth hormone (rhGH) monotherapy, followed by combination therapy with rhGH and gonadotropin-releasing hormone analog (GnRHa), and ultimately transitioned to GnRHa monotherapy. Her height SDS reached a peak of -0.19 during rhGH therapy. Following rhGH withdrawal, her height SDS dropped to -0.48 at 10 years and 7 months of age. Her body mass index (BMI) increased from 13.88 to 20.68 kg/m2 throughout the clinical course.

CONCLUSIONS

In children with EP300-mutated RTS and short stature, evaluation for GHD via growth hormone stimulation testing should be considered, as rhGH and GnRHa therapy is effective. However, in children with RTS who have not yet reached final adult height and retain residual growth potential, premature rhGH withdrawal may compromise acquired height benefits and exacerbate weight gain. Regular monitoring of growth velocity, pubertal progression, and metabolic parameters is essential to optimize long-term outcomes.