An Orthodenticle Homeobox 2 (OTX2) Mutation in a Patient With Combined Pituitary Hormone Deficiency, Pituitary Malformation, and Retinitis Pigmentosa

Cureus. 2023 Dec 20;15(12):e50819. doi: 10.7759/cureus.50819. eCollection 2023 Dec.

Abstract

Heterozygous mutations of orthodenticle homeobox 2 (OTX2)can result in ocular malformations, pituitary abnormalities, or hypopituitarism spanning from isolated growth hormone (GH) deficiency to combined pituitary hormone deficiency. We present a patient exhibiting growth and pubertal disturbances, developmental delay, and pigmentary retinopathy. Further examination revealed deficiencies in GH following clonidine stimulation, hypogonadism, and, subsequently, central hypothyroidism. Brain magnetic resonance imaging uncovered hypoplasia of the pituitary and an ectopic pituitary tissue. Sequence analysis of OTX2 identified a novel heterozygous mutation c.555_556dup, p.(Ser186Ilefs*21), indicative of a frameshift mutation. Replacement therapy with recombinant human GH, testosterone enanthate, and levothyroxine was started. Notably, GH therapy resulted in significant catch-up growth. This case report contributes to our comprehension of the molecular and clinical findings, particularly highlighting endocrine manifestations and a rare ophthalmologic manifestation associated with mutations in the OTX2 gene.

Keywords: combined pituitary hormone deficiency; hypopituitarism; neurodevelopment disorder; otx2 mutation; retinitis pigmentosa.

Publication types

  • Case Reports