ESPE Abstracts

Introduction: PKDCC gene mutation was first described in 2017, with ten patients described in the literature to date. It is associated with rhizomelic skeletal dysplasia, short stature, characteristic facial features of flat high forehead, hypertelorism, micrognathia and in some cases hearing loss. The clinical phenotype is expanding as confirmed cases emerge.

Case Description: We present two brothers born to non-consanguineous Caucasian parents, with antenatally diagnosed rhizomelic skeletal dysplasia. The first sibling was born at term with coloboma and aortic stenosis with a bicuspid aortic valve. Initial genetic work-up including parental trio exome sequencing was non-yielding. The second sibling born six years later was born at term with similar antenatal findings suggestive of skeletal dysplasia. At three weeks of life he presented very unwell, lethargic, dehydrated and poorly perfused and was found to be in adrenal crisis with sodium 116mmol/L, potassium 5.8mmol/L although normotensive with normal blood sugar. His cortisol was <30mmol/L. After stabilisation, he was initiated on glucocorticoid and mineralocorticoid replacement with sodium supplementation. Trio exome sequence on this patient, performed through CeGaT laboratory revealed one pathogenic and second likely pathogenic variant in the PKDCC gene in a compound heterozygous state. His brother subsequently tested positive for the same mutations but does not have adrenal insufficiency.

Discussion: Our two cases strengthen the existing phenotype in the literature that PKDCC mutation is associated with predominantly upper limb skeletal dysplasia with distinctive facial features. Coloboma, aortic valve abnormalities and adrenal insufficiency are new features not previously described in the literature for PKDCC gene mutation. Adrenal insufficiency is a potentially life threatening feature not previously described in this condition, which is important to consider in further PKDCC patients.

Conclusion: There are constant advancements in genetic diagnostics, our case highlights the importance of re-testing presumed genetic cases as new evidence emerges and new conditions are described. A diagnosis can provide an answer to families, contribute to prognostication and aid further family planning.