Phenotypic variability in children with growth hormone deficiency associated with posterior pituitary ectopia

Objective The cause of posterior pituitary ectopia (PPE) with anterior pituitary hormone deficiencies is unknown. This disease is usually considered sporadic. The objective of this study was to improve the phenotypic characterization of children with PPE and growth hormone deficiency (GHD) to seek insight into the mechanisms underlying abnormal pituitary-gland development. Patients and design Sixty children with GHD and PPE were evaluated in this retrospective chart review (1988-2003). Results Known extra-pituitary birth defects (BD) were present in 31 patients (BD+, 52%) and absent in 29 patients (BD-). Among BD+ patients, seven had well-defined syndromes (Fanconi anaemia, n = 2; Pallister-Hall, n = 1; Currarino, n = 2; or Stilling-Duane, n = 2) and the other 24 had 53 BDs, mainly involving the brain, eyes and the craniofacial structures (n = 27, 51%) but also affecting the heart, skeleton, kidneys, gastrointestinal tract and skin. Of the 60 patients, seven (12%) were born to consanguineous parents (five sporadic and two familial cases). There were seven (12%) familial cases, with wide variations in clinical presentation, endocrine profiles and magnetic resonance imaging (MRI) findings within families and various patterns consistent with autosomal dominant, recessive or X-linked transmission. Conclusion The high rate of extra-pituitary BDs and of familial components supports a role for genetic factors in the pathogenesis of this heterogeneous disorder. A detailed record of phenotypic abnormalities in patients with GHD and PPE might produce useful hypotheses for genetic studies.