Endocrine Abstracts

JOINT2813

Introduction: Noonan Syndrome (NS) is characterized by distinctive facial features, congenital heart disease, and short stature. Clinical presentation is highly variable, often leading to delayed diagnosis, which is sometimes only confirmed when affected family members exhibit more severe manifestations. NS is a relatively common cause of short stature, which may or may not be associated with growth hormone (GH) deficiency. In Portugal, NS is not yet an approved indication for GH treatment.

Case Report: We describe a family with at least two generations affected by NS. Two siblings from a fraternal set of three were referred to a Pediatric Endocrinology consultation due to short stature and suspected NS. Their father underwent GH treatment during childhood, although the underlying etiological study is unknown, and he reached a final height of 158 cm (SDS). The index case is the eldest daughter, a 3-year-old girl born with facial dysmorphisms, astigmatism, and motor coordination difficulties. Clinical evaluation highlighted severe short stature (-3.73 SDS) and distinctive facial features, including a high forehead and low-set ears. Her 2-year-old brother presented with pulmonary valve stenosis, patent foramen ovale, scoliosis, and similarly severe short stature (-4.54 SDS), with comparable facial features. Both had normal birth measurements. Analytical studies showed low IGF-1 levels, but GH stimulation tests demonstrated an adequate response. Genetic testing, including a familial segregation study, identified a heterozygous variant in the PTPN11 gene, likely pathogenic and consistent with their phenotypes. Since neither case presented a confirmed GH deficiency, GH therapy is not currently approved, and both children remain under periodic follow-up.

Discussion: NS is associated with short stature in approximately 50-70% of cases, either due to GH deficiency or dysfunction of the GH/IGF-1 axis. In this family, the father was unaware of his diagnosis, likely due to mild clinical manifestations aside from short stature. Given that NS is primarily inherited in an autosomal dominant manner, parental genetic testing is crucial for identifying other potentially affected relatives. As with Turner Syndrome, early initiation of GH therapy appears to improve final height outcomes. However, in Portugal, GH treatment is not yet approved for children with NS without confirmed GH deficiency. Considering the significant impact of short stature on future well-being, it is imperative that this indication grants approval for fully reimbursed GH treatment in our country.