National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Acrodysostosis


Other Names:
Arkless-Graham syndrome; Maroteaux-Malamut syndrome; Acrodysplasia; Arkless-Graham syndrome; Maroteaux-Malamut syndrome; Acrodysplasia; Nasal hypoplasia-peripheral dysostosis-intellectual disability syndrome; Peripheral dysostosis-nasal hypoplasia-intellectual disability (PNM) syndrome See More
Categories:
Acrodysostosis refers to a group of genetic disorders of bone growth. Common signs and symptoms include very short fingers and toes, underdeveloped facial bones, a small nose, and short stature. Many individuals with acrodysostosis have developmental delays and intellectual disability.[1][2][3] Individuals with acrodysostosis additionally may have hormone resistance, which means that the body does not respond to the certain hormones. There are two types of this disorder, characterized by the presence or absence of hormone resistance and the underlying genetic cause. Type 1 is caused by mutations in the PRKAR1A gene and may be associated with hormone resistance, whereas type 2 is caused by mutations in the PDE4D gene and is typically not associated with hormone resistance.[3] Both types are inherited in an autosomal dominant manner, with most reported cases occurring for the first time in a family due to a new mutation.[1][2][3] Acrodysostosis can be difficult to distinguish from pseudohypoparathyroidism and pseudopseudohypoparathyroidism.[1] While there is no cure for acrodysostosis, treatment is directed toward the specific symptoms in each individual and may require the coordinated efforts of a team of specialists.[2]
Last updated: 11/1/2016
The signs and symptoms found in individuals with acrodysostosis may include:[2][4]
  • Skeletal malformations: Short stature, short and malformed bones in the hands and feet, shortening of the bones in the arms and legs, abnormal curvature of the spine (scoliosis or kyphosis), and narrowing (stenosis) of the spaces within spine
  • Distinctive facial features: Underdevelopment of the upper jaw (maxillary hypoplasia), underdevelopment of the nasal bone (nasal hypoplasia), a flattened or depressed nasal bridge, widely-spaced eyes (hypertelorism), low-set ears, and an extra fold of skin that may cover the inner corners of the eyes (epicanthal folds)
  • Developmental delays and mild to moderate intellectual disability 
  • Resistance to multiple hormones including parathyroid hormone and thyroid stimulating hormone 
Additional findings may include repeated middle ear infections, hearing loss, obesity, skin lesions, blue eyes, and red or blond hair. In some males, the opening of the urethra is on the underside of the penis rather than the tip (hypospadias) and/or the testes may fail to descend into normal position in the scrotum (cryptorchidism).[2]
Last updated: 11/1/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal form of the vertebral bodies 0003312
Abnormality of the nail 0001597
Accelerated skeletal maturation
Advanced bone age
Early bone maturation
[ more ] 		0005616
Brachydactyly
Short fingers or toes
0001156
Cone-shaped epiphysis
Cone-shaped end part of bone
0010579
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ] 		0000457
Epiphyseal stippling
Speckled calcifications in end part of bone
0010655
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ] 		0000327
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Open mouth
Gaped jawed appearance
Gaped mouthed appearance
Slack jawed appearance
[ more ] 		0000194
Short metacarpal
Shortened long bone of hand
0010049
Short metatarsal
Short long bone of foot
0010743
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Short toe
Short toes
Stubby toes
[ more ] 		0001831
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
30%-79% of people have these symptoms
Abnormality of female external genitalia
Abnormal female external genitalia
0000055
Abnormality of immune system physiology 0010978
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Brachycephaly
Short and broad skull
0000248
Cryptorchidism
Undescended testes
Undescended testis
[ more ] 		0000028
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption
[ more ] 		0000684
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplasia of the radius
Underdeveloped outer large forearm bone
0002984
Hypoplasia of the ulna
Underdeveloped inner large forearm bone
0003022
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ] 		0000303
Micromelia
Smaller or shorter than typical limbs
0002983
Peripheral neuropathy 0009830
Spinal canal stenosis
Narrow spinal canal
0003416
5%-29% of people have these symptoms
Congenital hypothyroidism
Underactive thyroid gland from birth
0000851
Diabetes mellitus 0000819
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Hypogonadism
Decreased activity of gonads
0000135
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ] 		0001511
Irregular menstruation
Menstrual irregularity
0000858
Melanocytic nevus
Beauty mark
0000995
Mild short stature 0003502
Open bite
Absence of overlap of upper and lower teeth
Open bite between upper and lower teeth
[ more ] 		0010807
Percent of people who have these symptoms is not available through HPO
Autism 0000717
Autosomal dominant inheritance 0000006
Blue irides
Blue eyes
0000635
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose
[ more ] 		0000455
Broad palm
Broad hand
Broad hands
Wide palm
[ more ] 		0001169
Calvarial hyperostosis
Overgrowth of skullcap
0004490
Cone-shaped epiphyses of the phalanges of the hand
Cone-shaped end part of finger bones
0010230
Congenital onset
Symptoms present at birth
0003577
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches
[ more ] 		0000689
Dislocated radial head 0003083
Disproportionate short-limb short stature
Short limb dwarfism, disproportionate
Short-limbed dwarfism
[ more ] 		0008873
Elevated circulating parathyroid hormone level 0003165
Fair hair
Blond hair
Fair hair color
Flaxen hair color
Light colored hair
Sandy hair color
Straw colored hair
Towhead (hair color)
[ more ] 		0002286
Global developmental delay 0001263
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hyperactivity
More active than typical
0000752
Hypodontia
Failure of development of between one and six teeth
0000668
Hypoplastic vertebral bodies
Underdeveloped back bones
0008479
Hypospadias 0000047
Increased intracranial pressure
Rise in pressure inside skull
0002516
Long hallux
Long big toe
0001847
Malar flattening
Zygomatic flattening
0000272
Mild postnatal growth retardation 0001530
Narrow vertebral interpedicular distance 0008450
Neonatal epiphyseal stippling
Speckled calcifications in bone end parts in neonates
0005756
Obesity
Having too much body fat
0001513
Optic atrophy 0000648
Red hair
Red hair color
Red head (hair color)
[ more ] 		0002297
Round face
Circular face
Round facial appearance
Round facial shape
[ more ] 		0000311
Scoliosis 0002650
Short palm 0004279
Short phalanx of finger
Short finger bones
0009803
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
The prognosis (long-term outlook) for individuals with acrodysostosis is not known. This is due to the rarity of the disorder and the lack of articles in the medical literature with long-term follow-up.[4] The prognosis may differ depending on the underlying signs and symptoms present in each individual. 
Last updated: 11/1/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes brachydactyly type E, pseudohypoparathyroidism 1a or pseudopseudohypoparathyroidism.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.
  • The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Evaluation and Treatment of Skeletal Diseases which may be of interest to you.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Acrodysostosis. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Acrodysostosis:
    International Skeletal Dysplasia Registry (ISDR)
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    Acrodysostosis 1
    Acrodysostosis 2
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Acrodysostosis. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Silve C, Clauser E, Linglart A. Acrodysostosis. Horm Metab Res. 2012 Sep;44(10):749-58. Epub 2012 Jul 19; http://www.ncbi.nlm.nih.gov/pubmed/22815067. Accessed 11/1/2016.
  2. Prof. Agnès Linglart. Acrodysostosis. NORD. 2014; https://rarediseases.org/rare-diseases/acrodysostosis/. Accessed 11/1/2016.
  3. Mantovani G, Spada A, Elli FM. Pseudohypoparathyroidism and Gsa-cAMP-linked disorders: current view and open issues. Nat Rev Endocrinol. June 2016; 12(6):347-356. https://www.ncbi.nlm.nih.gov/pubmed/27109785.
  4. Dr Caroline SILVE. Acrodysostosis. Orphanet. August 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=950. Accessed 11/1/2016.