Unraveling genetic causes of congenital multiple pituitary hormone deficiencies

Congenital multiple pituitary hormone deficiency (MPHD) is a rare disorder with
an estimated incidence of 1 in 25,000 newborns. In contrast to most neonatal
screening programs worldwide, the Dutch neonatal screening program is able to
effectively detect neonates with this disorder.
In a previous large nationwide study our group showed that patients with
congenital MPHD show characteristic abnormalities on MRI of the
hypothalamic/pituitary region: ~75% have an ectopic posterior pituitary gland
(located in the floor of the third ventricle instead of in the sella turcica)
and an absent or thin pituitary stalk.
Although there has been much progress in the understanding of the embryonic
development of the anterior pituitary gland in terms of cell types and genes
involved, less than 5% of cases of congenital MPHD can be explained by
mutations in these genes. Since in most neonates with congenital MPHD the
anterior pituitary gland is not absent we hypothesize that the cause of MPHD is
not defective anterior pituitary gland development, but defective development
(or outgrowth) of the pituitary stalk and posterior pituitary gland and that
this defective development likely has a genetic cause.
The detection of genes causing congenital MPHD in patients with an ectopic
posterior pituitary gland and absent or thin pituitary stalk will enhance the
understanding of the molecular and cellular mechanisms leading to congenital
MPHD and also increase our understanding of pituitary development in man.
Modern molecular studies using next generation techniques searching for
variants in DNA derived from an affected individual and that from his/her
parents, usually allow finding the causative gene.

To find new genes causing congenital MPHD associated with the characteristic
MRI abnormalities of ectopic posterior pituitary gland and absent/thin
pituitary stalk.

Observational study with invasive measurements

There is no benefit of participating in this study for the participants. There
is a group benefit as the study will provide further insight in the genetic
causes of congenital MPHD.
The risks of this study are minimal for the participants. The burden is limited
to a single visit to the AMC and a single blood sampling.