Phenotypic Variability in a Family with Acrodysostosis Type 2 Caused by a Novel PDE4D Mutation Affecting the Serine Target of Protein Kinase-A Phosphorylation

Journal Title: Journal of Clinical Research in Pediatric Endocrinology - Year 2017, Vol 9, Issue 4

Abstract

Acrodysostosis is a very rare congenital multisystem condition characterized by skeletal dysplasia with severe brachydactyly, midfacial hypoplasia, and short stature, varying degrees of intellectual disability, and possible resistance to multiple G protein-coupled receptor signalling hormones. Two distinct subtypes are differentiated: acrodysostosis type 1 resulting from defects in protein kinase type 1-α regulatory subunit and acrodysostosis type 2 caused by mutations in phosphodiesterase 4D (PDE4D). Most cases are sporadic. We report on a rare multigenerational familial case of acrodysostosis type 2 due to a novel autosomal dominantly inherited PDE4D mutation. A 3.5-year-old boy presented with short stature, midfacial hypoplasia, severe brachydactyly, developmental delay, and behavioural problems. Laboratory investigations revealed mild thyrotropin resistance. His mother shared some characteristic features, such as midfacial hypoplasia and severe brachydactyly, but did not show short stature, intellectual disability or hormonal resistance. Genetic analysis identified the identical, novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in both patients. This case illustrates the significant phenotypic variability of acrodysostosis even within one family with identical mutations. Hence, a specific clinical diagnosis of acrodysostosis remains challenging because of great interindividual variability and a substantial overlap of the two subtypes as well as with other related Gsα-cAMP-signalling-linked disorders.

Authors and Affiliations

Julia Hoppmann, Caroline Silve, Chrystel Leroy, Astrid Bertsche, Franz Wolfgang Hirsch, Wieland Kiess, Roland Pfäffle, Volker Schuster

Keywords

Related Articles

A Novel Mutation of AMHR2 in Two Siblings with Persistent Müllerian Duct Syndrome

Persistent Müllerian Duct syndrome (PMDS) develops due to deficiency of anti-Müllerian hormone (AMH) or insensitivity of target organs to AMH in individuals with 46,XY karyotype. PMDS is characterized by normal male phen...

Time Trends, Regional Variability and Seasonality Regarding the Incidence of Type 1 Diabetes Mellitus in Romanian Children Aged 0-14 Years, Between 1996 and 2015

Objective: The incidence of type 1 diabetes mellitus in children is highly variable in the world. The aim of our study was to: 1) analyze the evolution of the incidence of childhood type 1 diabetes in Romania between 199...

Aromatase Deficiency due to a Novel Mutation in CYP19A1 Gene

Aromatase deficiency is a rare autosomal recessive genetic disorder with an unknown incidence. Aromatase converts androgens into estrogen in the gonadal and extra-gonadal tissues. Aromatase deficiency causes ambiguous ge...

Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study with 38,935 Infants

Objective: Congenital adrenal hyperplasia (CAH) is the most common form of primary adrenal insufficiency in children. Neonatal screening for CAH is effective in detecting the salt-wasting (SW) form and in reducing mortal...

Prospective Follow-up of Children with Idiopathic Growth Hormone Deficiency After Termination of Growth Hormone Treatment: Is There Really Need for Treatment at Transition to Adulthood?

Objectives: Continuation of growth hormone (GH) treatment in adolescents with severe childhood onset idiopathic GH deficiency (IGHD) during the transition period, irrespective of achievement of final height, is still deb...

Download PDF file
  • EP ID EP252180
  • DOI 10.4274/jcrpe.4488
  • Views 171
  • Downloads 0

How To Cite

Julia Hoppmann, Caroline Silve, Chrystel Leroy, Astrid Bertsche, Franz Wolfgang Hirsch, Wieland Kiess, Roland Pfäffle, Volker Schuster (2017). Phenotypic Variability in a Family with Acrodysostosis Type 2 Caused by a Novel PDE4D Mutation Affecting the Serine Target of Protein Kinase-A Phosphorylation. Journal of Clinical Research in Pediatric Endocrinology, 9(4), 360-365. https://europub.co.uk./articles/-A-252180