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
Remarkable Increase in the Prevalence of Overweight and Obesity Among School Age Children in Antalya, Turkey, Between 2003 and 2015
Objective: Childhood obesity (OB) is an acknowledged global problem with increasing prevalence reported around the world. We conducted this study with the aim of determining the local trend in OB and overweight (OW) prev...
Severe Early Onset Obesity due to a Novel Missense Mutation in Exon 3 of the Leptin Gene in an Infant from Northwest India
Monogenic obesity, caused by mutations in one of the genes involved in the control of hunger and satiety, is a rare cause of early onset obesity (EOO). The most common of the single gene alterations affect the leptin gen...
Subclinical Hypothyroidism in Danish Lean and Obese Children and Adolescents
Objective: Thyroid abnormalities are common in obese children. The aim of the present study was to examine the prevalence of subclinical hypothyroidism (SH) and to determine how circulating thyroid hormone concentrations...
Psychometric Properties of the Turkish Version of the University of Virginia Parent Low Blood Sugar Survey
Objective: The aim of this study was to produce and validate a Turkish version of the University of Virginia Parent Low Blood Sugar Survey (P-LBSS). The P-LBSS is used to assess parental fear of their diabetic children’s...
Evaluation of the Ovarian Reserve in Adolescents with Hashimoto’s Thyroiditis Using Serum Anti-Müllerian Hormone Levels
Objective: This study aims to evaluate ovarian reserve in adolescent girls with Hashimoto’s thyroiditis (HT) by assessment of serum anti-Müllerian hormone (AMH) levels. It was hypothesized that HT decreases ovarian reser...