Acrodysostosis

Title

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:

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases; Musculoskeletal Diseases See More

Summary Summary

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

Symptoms Symptoms

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
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 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
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		0002984
Hypoplasia of the ulna		0003022
Micromelia		0002983
Peripheral neuropathy		0009830
5%-29% of people have these symptoms
Congenital hypothyroidism		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
Melanocytic nevus	Beauty mark	0000995
Menstrual irregularities	Menstrual irregularity	0000858
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
Accelerated skeletal maturation	Advanced bone age Early bone maturation [ more ]	0005616
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
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
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		0000752
Hypodontia	Failure of development of between one and six teeth	0000668
Hypoplastic vertebral bodies		0008479
Hypospadias		0000047
Increased intracranial pressure		0002516
Long hallux	Long big toe	0001847
Malar flattening	Zygomatic flattening	0000272
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
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	Abnormal curving of the spine	0002650
Short metacarpal	Shortened long bone of hand	0010049
Short metatarsal	Short long bone of foot	0010743
Short palm		0004279
Short phalanx of finger	Short finger bones	0009803
Spinal canal stenosis	Narrow spinal canal	0003416
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486

Showing of 75 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2018

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

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.

Prognosis Prognosis

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

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

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 Research

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

International Skeletal Dysplasia Registry
UCLA-OHRC
Attn: Samantha Alon Najemy
615 Charles E. Young Drive
South, Room 410
Los Angeles, CA 90095-7358
Telephone: 310-825-8998
E-mail: Salon@mednet.ucla.edu
Web site: https://www.uclahealth.org/ortho/isdr

Greenberg Center for Skeletal Dysplasias
Johns Hopkins University
Institute of Genetic Medicine
600 North Wolfe Street
Blalock 1008
Baltimore, MD 21287
Telephone: 410-614-0977
E-mail: deedee@jhmi.edu
Website: http://www.hopkinsmedicine.org/institute-genetic-medicine/patient-care/genetics-clinic/about/greenberg-center-skeletal-dysplasia/

Organizations Organizations

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

European Skeletal Dysplasia Network
Institute of Genetic Medicine
Newcastle University
International Centre for Life
Central Parkway
New Castle upon Tyne
Manchester M13 9PT
NE1 3BZ, United Kingdom
E-mail: info@esdn.org
Website: http://www.esdn.org/eug/Home
International Osteoporosis Foundation
9, rue Juste-Olivier
CH-1260 Nyon
Switzerland
Telephone: +41 22 994 0100
Fax: +41 22 994 0101
E-mail: info@iofbonehealth.org
Website: http://www.iofbonehealth.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

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.

News & Events News & Events

News

NCATS Rare Diseases Are Not Rare! Challenge
October 9, 2018
The NIH Undiagnosed Diseases Network Expands
September 26, 2018

GARD Answers GARD Answers

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. Submit a new question

My sister was born with acrodysostosis. She has had health complications all her life. She is presently in the hospital with pericardial effusion and pleural effusion. Might this be associated with acrodysostosis? What is the life expectancy? See answer

Have a question? Contact a GARD Information Specialist.

References References

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.
Prof. Agnès Linglart. Acrodysostosis. NORD. 2014; https://rarediseases.org/rare-diseases/acrodysostosis/. Accessed 11/1/2016.
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.
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.