Acrodysostosis

ACRDYS1 is a hereditary autosomal dominant form of skeletal dysplasia characterized by short stature, severe BRACHYDACTYLY, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and OBESITY. Laboratory studies show resistance to multiple hormones, including PARATHYROID HORMONE; THYOTROPIN; CALCITONIN; GROWTH HORMONE-RELEASING HORMONE, and GONADOTROPIN in some patients. Mutations in the PRKAR1A gene have been identified. OMIM: 101800. ACRDYS2 is autosomal dominant and is characterized by brachydactyly, facial dysostosis, and SPINAL STENOSIS, as well as hormone resistance and INTELLECTUAL DISABILITY. It is caused by mutations in the PDE4D gene. OMIM: 614613

Also Known As:

Networked: 49 relevant articles (0 outcomes, 2 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Pseudohypoparathyroidism
2.	Brachydactyly
3.	Pseudopseudohypoparathyroidism
4.	Intellectual Disability (Idiocy)
5.	Acrodysostosis

Experts

1.	Silve, Caroline: 8 articles (12/2017 - 06/2011)
2.	Le Stunff, Catherine: 5 articles (08/2022 - 11/2015)
3.	Bougnères, Pierre: 4 articles (08/2022 - 06/2011)
4.	Mantovani, Giovanna: 4 articles (01/2019 - 12/2012)
5.	Linglart, Agnès: 4 articles (12/2018 - 06/2011)
6.	Motte, Emmanuelle: 4 articles (10/2017 - 06/2011)
7.	Clauser, Eric: 4 articles (02/2017 - 06/2011)
8.	Taylor, Susan S: 3 articles (10/2021 - 12/2016)
9.	Cormier-Daire, Valérie: 3 articles (01/2021 - 04/2012)
10.	Michot, Caroline: 3 articles (01/2021 - 04/2012)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Acrodysostosis:

1.	Hormones (Hormone)IBA 07/29/2014 - "A Chinese girl with acrodysostosis and concomitant multiple hormone resistance was recruited for our study. " 10/01/2020 - "Two genes have been associated with acrodysostosis with or without hormone resistance (PRKAR1A and PDE4D). " 01/01/2017 - "Modulation of signaling through GPCR-cAMP-PKA pathways by PDE4 depends on stimulus intensity: Possible implications for the pathogenesis of acrodysostosis without hormone resistance." 01/01/2016 - "The existence of hormone resistance is typical of the acrodysostosis type 1 syndrome. " 07/29/2014 - "Our findings further suggest that the c.866G>A/p.G289E mutation in the PRKAR1A gene may be the cause of acrodysostosis with concomitant multiple hormone resistance. "
2.	G-Protein-Coupled Receptors (Receptors, G Protein Coupled)IBA 09/01/2012 - "Recently, mutations of PRKAR1A and PDE4D downstream of GNAS on the cAMP-mediated G protein-coupled receptor (GPCR) signaling cascade have been identified in acrodysostosis with and without hormone resistance, although functional studies have been performed only for p.R368X of PRKAR1A. " 12/01/2012 - "Acrodysostosis is a rare skeletal dysplasia that is associated with multiple resistance to G protein-coupled receptor (GPCR) signaling hormones in a subset of patients. " 09/01/2012 - "PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance." 12/15/2017 - "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. "
3.	Cyclic AMP-Dependent Protein Kinases (cAMP-Dependent Protein Kinase)IBA 08/01/2022 - "Acrodysostosis is a rare skeletal dysplasia caused by loss-of-function mutations in the regulatory subunit of protein kinase A (PRKAR1A). " 10/15/2017 - "Our findings indicate that PDE4D3s carrying the ACRDYS2 mutations are more easily activated by protein kinase A-induced phosphorylation than WT PDE4D3. " 02/01/2017 - "Knock-In of the Recurrent R368X Mutation of PRKAR1A that Represses cAMP-Dependent Protein Kinase A Activation: A Model of Type 1 Acrodysostosis." 12/01/2012 - "Acrodysostosis is genetically heterogeneous because it results from heterozygous mutations in PRKAR1A or PDE4D, two key actors in the GPCR-cAMP-protein kinase A pathway. " 01/01/2023 - "Impaired cAMP processivity by phosphodiesterase-protein kinase A complexes in acrodysostosis."
4.	5-phenylpent-4-enyl-1-hydroperoxideIBA 06/01/1977 - "PHP and PPHP are probably differend manifestations of the same entity, and acrodysostosis may also be related to them. " 06/01/1977 - "The pattern profiles thus generated showed that those for PHP and PPHP are almost identical, and are similar to that seen in acrodysostosis, except for the much smaller size of the bones seen in the latter condition. " 01/01/2016 - "The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). " 11/21/2012 - "The literature describing acrodysostosis cases has been confusing because some reported patients may have had other phenotypically related diseases presenting with Albright Hereditary Osteodystrophy (AHO) such as pseudohypoparathyroidism type 1a (PHP1a) or pseudopseudohypoparathyroidism (PPHP). " 06/01/1977 - "The patterns of length alterations in the hand bones in cases of pseudohypoparathyroidism (PHP), pseudopseudohypoparathyroidism (PPHP), and acrodysostosis were evaluated. "
5.	Parathyroid Hormone-Related ProteinIBA 08/01/2023 - "Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD); acrodysostosis refers to iPPSD4 (acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (acrodysostosis type 2, due to PDE4D mutations). " 06/01/2018 - "Since PHP-related phenotypes are overlapping and other non GNAS-dependent disorders mimicking AHO, such as acrodysostosis, have been genetically characterized, the term PHP is today considered obsolete and better referred to the more comprehensive "inactivating PTH/PTHrP signaling disorder (iPPSD)" as proposed in a recent classification. " 01/01/2019 - "We highlight the value of expert radiological opinion and molecular testing in establishing correct diagnoses and discuss phenotypic features of our patients, including the first description of subcutaneous ossification and spina bifida occulta in PRKAR1A-related acrodysostosis, in the context of the novel inactivating PTH/PTH related peptide signaling disorder classification system." 01/01/2019 - "Identification of novel pathogenic variants and features in patients with pseudohypoparathyroidism and acrodysostosis, subtypes of the newly classified inactivating PTH/PTHrP signaling disorders." 12/01/2018 - "The increasing knowledge on these diseases made the actual classification of PHP outdated as it does not include related conditions such as acrodysostosis (ACRDYS) or progressive osseous heteroplasia (POH), so that a new nomenclature and classification has been recently proposed grouping these disorders under the term "inactivating PTH/PTHrP signaling disorder" (iPPSD). "
6.	Cyclic AMP (AMP, Cyclic)IBA 01/01/2013 - "PDE4D encodes a cyclic AMP regulator and places PDE4D-related acrodysostosis within the same family of diseases as pseudohypoparathyroidism, pseudopseudohypoparathyroidism, PRKAR1A-related acrodysostosis and brachydactyly-mental retardation syndrome; all characterized by cognitive impairment and short distal extremities." 11/01/2014 - "Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosis." 06/09/2011 - "We report a germ-line mutation in the gene encoding PRKAR1A, the cyclic AMP (cAMP)-dependent regulatory subunit of protein kinase A, in three unrelated patients with acrodysostosis and resistance to multiple hormones. " 01/01/2023 - "Mutations in the 3'5'cyclic AMP (cAMP)-dependent protein kinase (PKA) type I regulatory subunit isoform α (RIα) and phosphodiesterase (PDE) PDE4D have both been implicated in impaired PKA regulation in acrodysostosis. "
7.	Growth Hormone (Somatotropin)IBA 01/01/2020 - "Here in we report an adverse orthopedic outcome in a patient with ACRDYS1 with severe short stature treated with growth hormone. " 01/01/2020 - "Whereas growth hormone (GH) treatment has been studied in patients with PHP1a, the same is not true for the rarer ACRDYS1. " 08/01/2023 - "Growth patterns and outcomes of growth hormone therapy in patients with acrodysostosis." 01/01/2020 - "Legg-Calve-Perthes disease in an 8-year old girl with Acrodysostosis type 1 on growth hormone therapy: case report." 01/01/1995 - "Our sample included an initial group of 40 patients who had growth delay/constitutional delay of growth and puberty (n = 10), growth hormone insufficiency/deficiency (n = 15), low birth weight/Silver-Russell syndrome (n = 9), precocious puberty (n = 6), as well as 20 patients with various skeletal dysplasias (multiple epiphyseal dysplasia n = 7, pseudoachondroplasia n = 7, acrodysostosis n = 5, achondroplasia n = 1), 7 girls with Turner syndrome, and 10 boys with nephrotic syndrome on chronic corticosteroid treatment. "
8.	Phosphoric Diester Hydrolases (Phosphodiesterases)IBA 10/15/2017 - "Type 2 acrodysostosis (ACRDYS2), a rare developmental skeletal dysplasia characterized by short stature, severe brachydactyly and facial dysostosis, is caused by mutations in the phosphodiesterase (PDE) 4D (PDE4D) gene. " 01/01/2023 - "Impaired cAMP processivity by phosphodiesterase-protein kinase A complexes in acrodysostosis." 01/01/2017 - "In acrodysostosis without hormone resistance, a disease caused by phosphodiesterase (PDE)-4D mutations, increased PDE activity leads to bone developmental defects but with normal renal responses to PTH. " 01/01/2023 - "Mutations in the 3'5'cyclic AMP (cAMP)-dependent protein kinase (PKA) type I regulatory subunit isoform α (RIα) and phosphodiesterase (PDE) PDE4D have both been implicated in impaired PKA regulation in acrodysostosis. "
9.	Adenosine Diphosphate (ADP)IBA 02/17/2012 - "Transgene insertion in intronic sequences of Mdga2 gene shows methylation in an imprinted manner in an Acrodysplasia (Adp) mouse line." 11/23/2009 - "The insertional mouse mutation Adp (Acrodysplasia) confers a parent-of-origin developmental phenotype, with animals inheriting the mutation from their father showing skeletal abnormalities, whereas those inheriting the mutation from their mother are normal. " 12/01/1994 - "This chromosomal region contains three loci, Pax9, Tcf3a, and Acrodysplasia (Adp), which seem to play an important role in pattern formation during mouse embryogenesis. " 12/01/1994 - "Fine genetic mapping defines the genetic order of Pax9, Tcf3a, and Acrodysplasia (Adp)." 02/17/2012 - "The Acrodysplasia (Adp) mutation arises from the insertion of a transgene containing a mouse metallothionein-promoted bovine papilloma virus and human growth hormone-releasing factor gene. "
10.	HoloenzymesIBA 12/04/2016 - "While CNC mutations cause increased PKA activity, ACRDYS1 mutations result in decreased PKA activity and cAMP resistant holoenzymes. " 10/01/2021 - "Although genetic mutations in the PKA holoenzyme are known to cause diseases such as Carney complex, Cushing syndrome, and acrodysostosis, the story largely stops there. "

Therapies and Procedures

1.	Therapeutics 01/01/2020 - "Patients with ACRDYS1 on GH therapy may be at increased risk of LCPD. " 08/01/2023 - "Growth patterns and outcomes of growth hormone therapy in patients with acrodysostosis." 01/01/2020 - "Legg-Calve-Perthes disease in an 8-year old girl with Acrodysostosis type 1 on growth hormone therapy: case report."
2.	Laminectomy 01/01/2022 - "Laminectomy as treatment for abrupt neurological decline in acrodysostosis: A case report." 01/01/2001 - "Spinal stenosis is an underappreciated risk in acrodysostosis, despite the reported loss of normal caudal widening of the lumbar interpediculate distance on AP spine radiographs in the original report of this disorder by Robinow et al., with confirmation of these radiographic findings by Butler et al. We report two sporadic cases of acrodysostosis, one of which required decompressive laminectomy for symptomatic spinal stenosis, and review 11 cases of acrodysostosis from 9 families that were submitted to the International Skeletal Dysplasia Registry. "
3.	Osteotomy 04/01/2021 - "Shortening Scarf Osteotomy for Macrodactyly and Valgus of the Hallux in Acrodysostosis Lesser Toes Brachydactyly."