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Disease Profile

Acrodysostosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q75.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Arkless-Graham syndrome; Maroteaux-Malamut syndrome; Acrodysplasia;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases;

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]

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]

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.

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.
    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
    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.

    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

      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.

          References

          1. Silve C, Clauser E, Linglart A. Acrodysostosis. Horm Metab Res. 2012 Sep;44(10):749-58. Epub 2012 Jul 19; https://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; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=950. Accessed 11/1/2016.

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