ESPE Abstracts

Background: Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) is a rare genetic condition caused by de novo mutations in the KAT6B gene, which encodes lysine acetyltransferase 6B, an enzyme involved in chromatin modification. The clinical phenotype is characterized by global developmental delay and multiple congenital abnormalities, including a number of distinctive facial features (ptosis, blepharophimosis, and mask-like appearance), skeletal involvement (hypoplastic or displaced patellas), and genital abnormalities, such as cryptorchidism. In addition, hypotonia, dental malformations, thyroid abnormalities (congenital hypothyroidism and thyroid agenesis), hearing loss, and congenital heart defects may occur in these patients. Hashimoto's thyroiditis is a rare association; in fact, no cases are reported in the literature.

Case Presentation: An 8-year-old Caucasian child referred to our Pediatric Endocrinology Outpatient Clinic for acquired hypothyroidism. In the first months of life, he developed a condition of overt nonautoimmune hypothyroidism, for which levothyroxine replacement therapy (LT4) was started. Newborn screening for congenital hypothyroidism was negative, and annual thyroid ultrasound scans were normal. At age of 4 years, a series of genetic investigations were performed for the presence of mental retardation, acquired hypothyroidism, cryptorchidism, and dysmorphisms. Say-Barber-Biesecker-Young-Simpson syndrome was diagnosed, and a multispecialty follow-up was initiated, which included periodic evaluation of thyroid function and ultrasonography. His clinical phenotype was characterized by intellectual disability, global developmental delay, and dysmorphic traits, such as blepharophimosis, epicanthus, long thumbs, and low set ears. On clinical examination, no evidence of goiter was observed. Height (121.3 cm; -1.20 SDS), weight (24 kg; -0.47 SDS) and body mass index (16.31 kg/m2; -0.24 SDS) were normal for sex and age. No signs of pubertal development were present.

Results: Laboratory examination showed normal thyroid function under LT4 treatment. On thyroid ultrasonography, diffuse parenchymal inhomogeneity with pseudonodular areas and enhanced vascularization were observed. Marked positivity of antireoglobulin and antireoperoxidase antibodies, suggestive of autoimmune thyroiditis, was detected. TSH receptor antibody assay was negative. A diagnosis of Hashimoto's thyroiditis was made in the context of SBBYS syndrome.

Conclusions: Our case is the first report of chronic lymphocytic thyroiditis in a patient with SBBYS syndrome. Abnormalities of thyroid structure or function are a common finding in these subjects, but there are no data on the presence of autoimmune thyroid diseases. For this reason, evaluation of thyroid autoimmunity should be included in the diagnostic workup of this syndrome, even in the presence of an already known condition of hypothyroidism.