ESPE Abstracts (2016) 86 P-P2-771

Compound Heterozygosity for Two Novel POU1F1 Mutations in Siblings with Isolated Childhood Onset Growth Hormone Deficiency (CO-GHD)

Mariana Gracea,b, Mato Nagelc, Caroline Joyceb, Rose Morisseyb & Susan O’Connellb


aUniversity College Cork, Cork, Ireland; bCork University Hospital, Cork, Ireland; cLaboratory for Molecular Diagnostics Center for Nephrology and Metabolic Disorders, Werner-Seelenbinder, Germany


Background: CO-GHD can be caused by a variety of aetiologies, including pituitary or brain structural abnormalities, and increasingly recognised genetic mutations of pituitary transcription factors. Idiopathic GHD is a diagnosis of exclusion. POU1FI is a late pituitary transcription factor. Mutations of POU1F1 have autosomal recessive (AR) inheritance, and phenotypically present with a normal or small anterior pituitary gland on magnetic resonance imaging (MRI), they are associated with GH, prolactin and variable TSH deficiency.

Objective and hypotheses: To describe the clinical history of two siblings diagnosed with CO-GHD from their diagnosis until the completion of growth of the older sibling, and the results of genetic investigations.

Method: A retrospective description of two siblings with CO-GHD.

Results: The boy was diagnosed with GHD at the age of 5.4 years, presenting with severe short stature (Height SDS −4.1). Excellent response to recombinant GH (r GH) was seen with a final height (−0.19 SD) within genetic target. At age 17 years insulin tolerance test, confirmed persistent GHD. His younger sister presented with neonatal hypoglycaemia associated with a low GH level and low IGF-1 SDS. Growth failure was noted by the age of 2 months (length SDS was −3.35). She has responded to rGH with a current height SDS is −1.19 SD at age 3 years. Pituitary MRI and thyroid function in both siblings were normal. Given the similar phenotypes within the same family investigations were undertaken which identified two novel genetic mutations of POU1F1 in exon 3 and 4- p.K166E and P.E224K respectively.

Conclusion: The phenotype of early presentation of severe GHD is consistent with previously reported cases of POU1F1 mutations. As CO-GHD is rare, reoccurrence within the same family should prompt genetic investigation to explain the underlying aetiology, to guide on surveillance for other hormonal deficiencies, and to help predict persistence of GHD into adulthood.

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