ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 50 CC01 | DOI: 10.1530/endoabs.50.CC01

Novel ABCC9 mutation with Cantu syndrome-associated phenotype of hypertrichosis with acromegaloid facial features (HAFF) with coexisting familial pituitary adenoma

Pedro Marques1, Amy Ronaldson1, Rupert Spencer1, Patrick Morrison2, Ian Carr3, Mary Dang1, David Bonthron3, Steven Hunter4 & Márta Korbonits1

1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 2Department of Medical Genetics, Belfast HSC Trust, Belfast, United Kingdom; 3School of Medicine,
St James’s University Hospital, University of Leeds, Leeds, United Kingdom; 4Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Belfast, United Kingdom.

Pseudoacromegaly or acromegaloidism is used to describe cases where acromegaly-related physical appearance can be observed without any abnormality in the growth hormone (GH) axis. Acromegalic features, in particular coarse facies, together with hypertrichosis, are typical manifestations of one of the pseudoacromegaly conditions: hypertrichosis acromegaloid facial features (HAFF) syndrome. This condition phenotypically overlaps with Cantu syndrome and acromegaloid facial appearance (AFA) syndrome.

We present a three-generation family with five affected members with Cantu/HAFF syndrome, displaying marked acromegalic facies and prominent hypertrichosis, due to a missense mutation in the ABCC9 gene. The proband, a girl aged 2 years-old, was referred to the Dermatology department due to marked generalised hypertrichosis, soon noticed after birth, in association with coarsening of her facial appearance. Her height was just below the 97th centile, and her endocrine assessment, including GH axis, was normal. Proband’s father, paternal aunt and half sibling were referred to the Endocrine department for formal exclusion of acromegaly, they also had hypertrichosis. While GH axis was normal, two of them have non-functioning pituitary macroadenomas, a feature that has not been previously associated with Cantu/AFA/HAFF syndromes. The proband’s father had recurrent pericardial effusions; cardiac involvement is known to be present in Cantu syndrome.

Activating mutations in ABCC9, and less commonly in the KCNJ8 gene, two subunits of a ATP-sensitive potassium channel, have been linked with these conditions. There is no clear explanation for the mechanism acromegaloid features/hypertrichosis by activation of this channel. Remarkably, however, minoxidil, a well-known ATP-sensitive potassium channel agonist, can cause similar phenotype of hypertrichosis and acromegaloid facial features. This family raises awareness for this complex group of conditions, in particular endocrinologists and paediatric endocrinologists, who are likely to be referred to adult or paediatric endocrinologists as part of evaluation for acromegaloid features. The link with pituitary adenomas is currently unclear.