Background and aim: The development of the pituitary gland is closely linked to this of the eyes and forebrain, as they all originate from the same embryonic origin, the anterior neural ridge. The constellation of symptoms leading to septo-optic dysplasia (SOD) is well established; other ophthalmic signs may be under-reported. The aim of the study was to define if patients with hypopituitarism present with eye abnormalities, which are distinct from SOD, and if this association could help the genetic diagnosis of the condition.
Methods: We studied case records of patients referred over the last 10 years from national and international centres.
Results: We identified 96 patients with hypopituitarism (male:female 1.2:1), who had eye abnormalities that were distinct from SOD. Hypopituitarism was familial in 14.5% (n=14) and in 5.2%, patients were of consanguineous pedigrees. The spectrum of eye abnormalities included: colobomas not associated with CHARGE syndrome (n=11, 1.5%), pigmented disorders of the retina (n=4, 4.2%), retinal dysplasia (n=13, 13.5%), congenital cataracts, (n=3, 3.5%), amaurosis (n=3, 3.5%), anophthalmia or microphthalmia (n=32, 33.3%). Other eye abnormalities (n=30, 31.2%), ranged from glaucoma to blepharophimosis, staphylomas and atypical appearance of the optic discs. In four cases with retinal pigment defects or retinal dysplasia there was a single pituitary hormone deficiency, isolated GHD (n=2) or ACTHD (n=2). In all other cases, retinal abnormalities were associated with multiple pituitary hormone deficiencies. SOX2 mutations were identified in 40% (13/32) of patients with anophthalmia or microphthalmia and they all had gonadotrophin deficiency; we identified a novel OTX2 mutation (p.E79X) in one a patient. We found no mutations in HESX1, GH1, SIX3, PAX6 or SOX3 in this cohort.
Conclusions: Patients with hypopituitarism may present with variable eye abnormalities. Monitoring for pituitary hormone deficiencies is recommended in children with congenital eye abnormalities. The study of the association of eye and pituitary abnormalities may help to identify novel genes implicated in pituitary development.