An emerging, recognizable facial phenotype in association with mutations in GLI-similar 3 (GLIS3)

Area of Science:

• Genetics
• Endocrinology
• Pediatrics

Background:

• Neonatal diabetes and hypothyroidism (NDH) syndrome, linked to GLIS3 gene mutations, was initially described in 2003.
• Previous reports noted neonatal diabetes, hypothyroidism, and variable liver, kidney, and eye involvement.
• Detailed facial dysmorphism descriptions were lacking in prior NDH syndrome studies.

Purpose of the Study:

• To describe the common facial dysmorphisms in a cohort of seven patients with GLIS3 mutations.
• To report the emergence of a distinct facial gestalt in individuals with GLIS3 mutations.
• To characterize the evolution of facial features associated with NDH syndrome.

Main Methods:

• Clinical evaluation of seven patients with confirmed GLIS3 mutations.
• Detailed documentation of facial features, including ear position, nasal bridge, palpebral fissures, and philtrum.
• Comparative analysis of facial characteristics across the cohort and with previous descriptions.

Main Results:

• A consistent facial gestalt was observed, including bilateral low-set ears, depressed nasal bridge with overhanging columella, elongated upslanted palpebral fissures, and a long philtrum with a thin upper lip vermilion border.
• These facial features were present in all seven patients with GLIS3 mutations.
• The facial gestalt appeared to evolve and become more recognizable with age.

Conclusions:

• GLIS3 mutations are associated with a distinct and recognizable facial gestalt in patients with NDH syndrome.
• The identification of this facial gestalt aids in the clinical recognition and diagnosis of GLIS3-related disorders.
• Further research is warranted to understand the developmental basis of this facial phenotype.