ESPE Abstracts

Background: Pituitary gland duplication is a very rare developmental abnormality. It is often associated with other midline anomalies including cleft palate, spinal cord and corpus callosum defects, termed duplication of the pituitary gland-plus syndrome. Of the only 40 cases reported in the literature, most are in females and are often associated with precocious puberty. Duplication of the pituitary gland may arise from blastogenesis defects, with splitting of the rostral end of the notochord, though the exact mechanism is still unclear. Thus far no causative genetic mutations have been found. This is the largest case series that has been described.

Case Series: 8 patients, 4 male, from 4 centres in Europe with duplication of the pituitary gland. Half also had duplication of the pituitary stalk and some had duplication of mammillary bodies, basilar artery (n = 3) or nasal septum. All had other anomalies including a palate abnormality (cleft n = 5, high arched n = 1), dermoid cyst (nasal n = 3, palate n = 1), hamartoma (third ventricle n = 1, soft palate n = 1) teratoma (nasopharynx n = 1, palatine n = 1) and persistent craniopharyngeal duct (n = 2). One patient had a partial agenesis of the corpus callosum with a midline brain lipoma, and duplicated thyroglossal cyst. Spinal column defects were seen in three patients including cervical cleft, and another with an Arnold Chiari malformation and myelomeningocele. Three female cases and one male had precocious puberty. Another male patient had undescended testes with partial hypogonadotropic hypogonadism and partial growth hormone deficiency. Hearing impairment primarily from chronic ear infections occurred in 38% of patients. Half of the patients had visual impairment, with two patients having optic nerve hypoplasia, and another with possible small optic discs. Four patients were diagnosed with mild learning difficulties, and of these patients, two had seizures and sleep problems. A patent ductus arteriosus and patent foramen ovale were the only cardiac abnormalities reported. There was one death in this cohort in early childhood, and the eldest are now in their third decade. Six of the 8 children underwent whole exome sequencing (with trio analysis in 5 patients), but no relevant genetic variants were identified.

Conclusion: This case series highlights the phenotypic spectrum associated with duplication of the pituitary gland. This will be informative for the patient, their family, and the clinicians to highlight the possible associated pathology, and to direct their management. Future research should be directed towards ongoing collaboration to further characterise this syndrome, and to discover possible aetiological factors.