Acrodysostosis is a rare

congenital malformation A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

syndrome which involves shortening of the interphalangeal

joints A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

of the

hands A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the koala (which has two opposable thumbs on each "han ...

and

feet The foot (: feet) is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is an organ at the terminal part of the leg made up of ...

intellectual disability Intellectual disability (ID), also known as general learning disability (in the United Kingdom), and formerly mental retardation (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

in approximately 90% of affected children, and peculiar

facies In geology, a facies ( , ; same pronunciation and spelling in the plural) is a body of rock with distinctive characteristics. The characteristics can be any observable attribute of rocks (such as their overall appearance, composition, or con ...

. Other common abnormalities include short head (as measured front to back), small broad upturned

nose A nose is a sensory organ and respiratory structure in vertebrates. It consists of a nasal cavity inside the head, and an external nose on the face. The external nose houses the nostrils, or nares, a pair of tubes providing airflow through the ...

with flat

nasal bridge The nasal bridge is the upper part of the nose, where the nasal bones and surrounding soft tissues provide structural support. While commonly discussed in human anatomy, nasal bridges exist in various forms across many vertebrates, particularl ...

, protruding jaw, increased

bone age Bone age is the degree of a person's skeletal development. In children, bone age serves as a measure of physiological maturity and aids in the diagnosis of growth abnormalities, endocrine disorders, and other medical conditions. As a person grows ...

intrauterine growth retardation Intrauterine growth restriction (IUGR), or fetal growth restriction, is the poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's b ...

juvenile arthritis Childhood arthritis (juvenile arthritis or pediatric rheumatic disease) is an umbrella term used to describe any rheumatic disease or chronic arthritis-related condition which affects individuals under the age of 16. There are several subtypes tha ...

and

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ...

. Further abnormalities of the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

genitals A sex organ, also known as a reproductive organ, is a part of an organism that is involved in sexual reproduction. Sex organs constitute the primary sex characteristics of an organism. Sex organs are responsible for producing and transporting ...

teeth A tooth (: teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...

, and

skeleton A skeleton is the structural frame that supports the body of most animals. There are several types of skeletons, including the exoskeleton, which is a rigid outer shell that holds up an organism's shape; the endoskeleton, a rigid internal fra ...

may occur. Other common abnormalities include short head (as measured front to back), small broad upturned

with flat

, protruding jaw, increased

and

. Further abnormalities of the

, and

may occur.

Signs and Symptoms

Acrodysostosis presents with a wide spectrum of clinical manifestations. The following is a list of conditions and complications associated with acrodysostosis.

Bone issues

* Skeletal dysplasia (dwarfism, short stature) * Brachydactyly * Advanced bone age * Bone plate fusing * Scoliosis * Pain – joint, hip, lower back, wrist

Endocrine

* Hypothyroidism * Hypoparathyroidism * Pseudohypoparathyroidism * Vitamin D deficiency * Thyroid cysts * Type 1 diabetes

Behavioural / Developmental / Emotional

* Autism Spectrum Disorder (ASD) * Childhood Apraxia of Speech * Cognitive impairment * Sensory issues * Gross motor delays * Fine motor delays

Craniofacial and dental

* Cranial frontal nasal syndrome Midface hypoplasia * Depressed nasal bridge * Retrognathia * Glossoptosis * High palate * Mandibular distraction surgery Jaw surgery * Underbite * Chalky teeth * Overcrowded teeth * Early eruption of adult teeth * Small, unaligned teeth

Cardiology

* Hypertension * Atrial Septal Defect (ASD) * Aortic Coarctation * Middle Aortic Syndrome (MAS) Coarctation of abdominal aorta Bradycardia * Bicuspid aortic valve

Causes

Acrodysostosis is believed to be caused by mutations in the PRKAR1A gene (type 1) or the PDE4D gene (type 2). It has been suggested that the condition might be

genetically Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar workin ...

related i.e. in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

mode of

transmission Transmission or transmit may refer to: Science and technology * Power transmission ** Electric power transmission ** Transmission (mechanical device), technology that allows controlled application of power *** Automatic transmission *** Manual tra ...

. Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception. A

PRKAR1A cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the ''PRKAR1A'' gene. Function cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by act ...

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

has been identified in acrodysostosis with

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

resistance.

Diagnosis

Treatment

There are currently no approved treatments or standardised treatment guidelines for acrodysostosis. Management of acrodysostosis typically focuses on addressing specific symptoms that occur in each individual and may include surgery, physical therapy and special education.

Research

A number of transgenic mouse models have been generated that harbour genetic mutations within genes linked to the condition in humans. These mouse models exhibit phenotypes similar to that observed in Acrodysostosis in humans.

Media

The actress

Olivia Colman Sarah Caroline Sinclair ( Colman; born 30 January 1974), known professionally as Olivia Colman, is an English actress. She has received various accolades, including an Academy Award, four BAFTA Awards, two Emmy Awards, three Golden Globe Award ...

partnered with the charit
Acrodysostosis Support and Research
to raise awareness for the disease. She participated in a promotional video campaign in December 2020.

References

External links

* * * {{Medical resources , DiseasesDB = 31405 , ICD10 = Q75.4 , ICD9 = , ICDO = , OMIM = 101800 , MedlinePlus = 001248 , eMedicineSubj = , eMedicineTopic = , MeshID = C538179 , Orphanet = 950 Congenital disorders Rare diseases Syndromes with craniofacial abnormalities