INTRODUCTION: Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) mutations cause early-onset immune dysregulation syndrome, characterized by multi-organ autoimmunity and lymphoproliferation. The onset age of interstitial lung disease (ILD) is later in childhood and substantially later than other clinical phenotypes. We report a patient with ILD and syndromic characteristics.
CASE REPORT: A 4-years-old girl with a history of congenital hypothyroidism, clubbing skeletal dysplasia, arthrogryposis, delayed psychomotor development, short stature, syndactyly, rhizomelic shortening of the limbs, and deviation of the radius/ulna and longstanding snoring. Otherwise, she had a completely normal life. A polysomnography revealed significant chronic hypoxemia (saturation less than 90%). Chest computed tomography (CT) showed interstitial-alveolar infiltrate, with multiple simple cysts and bilateral nodules consistent with lymphoid interstitial pneumonia. An abdominal ultrasound demonstrated hepatomegaly and splenomegaly. She had no history of recurrent infections, autoimmune diseases, family history of Inborn Error of Immunity (IEI) or consanguinity. Immunoglobulin levels, lymphocyte subpopulations, regulatory T lymphocytes, lymphocyte proliferation, and tetanus toxoid antibodies were normal. Th17 lymphocytes are pending. Autoimmunity study was negative. Exome showed probable pathogenic mutation in STAT3 gene (c.1243G>A p.(Glu415Lys)). She was diagnosed as having a STAT-3 GOF, even though there is no evidence of functional study for this variant in the literature. She is undergoing lymphoproliferative studies to discard neoplasias, without new infections or autoimmune diseases. Currently with oxygen therapy planning to use Ruxolitinib as soon as possible.
DISCUSSION: We present a case of childhood-onset lung disease associated with syndromic features that probably correspond to STAT3 GOF mutation. To date, there is only one report in the literature of the same mutation in the STAT3 gene, but no functional study was performed for this genetic variant.