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Disease Profile

Pycnodysostosis

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.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

Q78.8

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.

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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)

Pyknodysostosis; PKND; PYCD

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases

Summary

Pycnodysostosis impacts bone growth and is present from birth. Symptoms include a large head and high forehead, undeveloped facial bones, and short fingers and toes. People with pycnodysostosis may have short stature, dental abnormalities, brittle bones, and delayed closure of the skull bones. Bones may become more brittle with age. Other complications like trouble breathing during sleep (sleep apnea) and bone infections may occur. Pycnodysostosis is caused by a CTSK gene that is not working correctly and inherited in an autosomal recessive pattern. The diagnosis of pycnodysostosis is based on clinical examination and X-ray findings, and is confirmed by genetic testing. Treatment is based on managing the symptoms.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with pycnodysostosis. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[2][3]

  • Short bones
  • Loss of bone tissue from the hands (acro-osteolysis)
  • Delayed closure of the skull bones
  • Underdeveloped facial bones
  • Thickening of the face and skull bones
  • Dental anomalies

Many of the signs of pycnodysostosis are present at birth. People with pycnodysostosis are usually shorter than average and have normal intellectual development. Bone infections (osteomyelitis) and trouble breathing during sleep (sleep apnea) may also occur. The bones often get more brittle with time.[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.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal clavicle morphology
Abnormal collarbone
0000889
Abnormal fingernail morphology
Abnormal fingernails
Abnormality of the fingernails

[ more ]

0001231
Abnormal pelvis bone ossification
0009106
Abnormal vertebral morphology
0003468
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Brachycephaly
Short and broad skull
0000248
Brachydactyly
Short fingers or toes
0001156
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Frontal bossing
0002007
High forehead
0000348
Malar flattening
Zygomatic flattening
0000272
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Narrow palate
Narrow roof of mouth
0000189
Osteolysis
Breakdown of bone
0002797
Persistent open anterior fontanelle
0004474
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Short distal phalanx of finger
Short outermost finger bone
0009882
Short stature
Decreased body height
Small stature

[ more ]

0004322
Short toe
Short toes
Stubby toes

[ more ]

0001831
Skeletal dysplasia
0002652
30%-79% of people have these symptoms
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth

[ more ]

0006482
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Bone pain
0002653
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Ridged nail
Grooved nails
Nail ridging

[ more ]

0001807
Wormian bones
Extra bones within cranial sutures
0002645
5%-29% of people have these symptoms
Abnormal pattern of respiration
Abnormal respiratory patterns
Unusual breathing patterns

[ more ]

0002793
Abnormality of the skin
0000951
Anemia
Low number of red blood cells or hemoglobin
0001903
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Hepatomegaly
Enlarged liver
0002240
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hyperlordosis
Prominent swayback
0003307
Kyphosis
Hunched back
Round back

[ more ]

0002808
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Osteomyelitis
Bone infection
0002754
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Abnormal thorax morphology
Abnormality of the chest
0000765
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
0002644
Absent frontal sinuses
0002688
Autosomal recessive inheritance
0000007
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Delayed eruption of permanent teeth
Delayed eruption of adult teeth
0000696
Delayed eruption of primary teeth
Delayed eruption of baby teeth
Delayed eruption of milk teeth
Late eruption of baby teeth
Late eruption of milk teeth

[ more ]

0000680
Hypodontia
Failure of development of between one and six teeth
0000668
Increased bone mineral density
Increased bone density
0011001
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Osteolytic defects of the distal phalanges of the hand
0009839
Persistence of primary teeth
Delayed loss of baby teeth
Failure to lose baby teeth
Retained baby teeth

[ more ]

0006335
Prominent nose
Big nose
Disproportionately large nose
Increased nasal size
Increased size of nose
Large nose
Pronounced nose

[ more ]

0000448
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Scoliosis
0002650
Spondylolisthesis
Displacement of one backbone compared to another
Slipped backbone

Cause

Pycnodysostosis occurs when the CTSK gene is not working correctly.[3] DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.

Diagnosis

Pycnodysostosis is diagnosed through a clinical examination, the symptoms, and X-rays of the affected bones. Genetic testing may be used to confirm the diagnosis.[2]

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.

Treatment

The treatment for pycnodysostosis is based on managing the symptoms. Treatment may include surgery, dental procedures, and medications for pain.[2][3]

Specialists involved in the care of someone with pycnodysostosis may include:

  • Orthopedist
  • Dentist
  • Otolaryngologist
  • Orthodontist
  • Maxillofacial surgeon

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

  • 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. 
  • 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 Pycnodysostosis. Click on the link to view a sample search on this topic.

References

  1. Farronato G, Salvadori S, Nolet F, Borgonovo A, Esposito L. Pycnodysostosis: review and case report. Minerva Stomatol. 2014; 63(6):229-237. https://pubmed.ncbi.nlm.nih.gov/25267152.
  2. Bizaoui V, Michot C, Baujat G, et al. Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review. Clin Genet. 2019; 96(4):309-316. https://pubmed.ncbi.nlm.nih.gov/31237352.
  3. Gray ML, Su A, Cruciata G, Som PM. Pycnodysostosis in an Adult: A Case Report and Review of the Literature. Ear Nose Throat J. 2019; 98(10):627-628. https://pubmed.ncbi.nlm.nih.gov/31847556.
  4. de Oliveira EM, de Arruda JAA, Nascimento PAM, Neiva IM, Mesquita RA, Souza LN. An Update on Osteomyelitis Treatment in a Pycnodysostosis Patient. J Oral Maxillofac Surg. 2018; 76(10):2136.e1-2136.e10. https://pubmed.ncbi.nlm.nih.gov/30030999.
  5. Markatos K, Mavrogenis AF, Karamanou M, Androutsos G. Pycnodysostosis: the disease of Henri de Toulouse-Lautrec. Eur J Orthop Surg Traumatol. 2018; 28(8):1569-1572. https://pubmed.ncbi.nlm.nih.gov/29797092.
  6. Khoja A, Fida M, Shaikh A. Pycnodysostosis with Special Emphasis on Dentofacial Characteristics. Case Rep Dent. 2015 Nov 16; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663328/.

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