Cleidocranial dysostosis

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Cleidocranial dysostosis
Other namesCleidocranial dysplasia, [1] Marie-Sainton syndrome, [1] mutational dysostosis [2]
Specialty Medical genetics
Symptoms Missing collarbone, prominent forehead, flat nose, shorter [1]
Usual onsetPresent at birth [3]
CausesGenetic (RUNX2 gene) [1]
Diagnostic method Based on symptoms and X-rays, confirmed by genetic testing [4]
Differential diagnosis Mandibuloacral dysplasia, pyknodysostosis, osteogenesis imperfecta, Hajdu-Cheney syndrome [5]
Treatment Supportive care [5]
Prognosis Normal life expectancy [3]
FrequencyOne per million people [1]

Cleidocranial dysostosis (CCD), also called cleidocranial dysplasia, is a birth defect that mostly affects the bones and teeth. [1] The collarbones are typically either poorly developed or absent, which allows the shoulders to be brought close together. [1] The front of the skull often does not close until later, and those affected are often shorter than average. [1] Other symptoms may include a prominent forehead, wide set eyes, abnormal teeth, and a flat nose. [1] Symptoms vary among people; however, intelligence is typically unaffected. [1]

Contents

The condition is either inherited or occurs as a new mutation. [1] It is inherited in an autosomal dominant manner. [1] It is due to a defect in the RUNX2 gene which is involved in bone formation. [1] Diagnosis is suspected based on symptoms and X-rays with confirmation by genetic testing. [4] Other conditions that can produce similar symptoms include mandibuloacral dysplasia, pyknodysostosis, osteogenesis imperfecta, and Hajdu-Cheney syndrome. [5]

Treatment includes supportive measures such as a device to protect the skull and dental care. [5] Surgery may be performed to fix certain bone abnormalities. [4] Life expectancy is generally normal. [3]

It affects about one per million people. [1] Males and females are equally commonly affected. [5] Modern descriptions of the condition date to at least 1896. [6] The term is from cleido meaning collarbone, cranial from the Greek κρανίο meaning skull, and dysostosis meaning formation of abnormal bone. [7]

Signs and symptoms

Cleidocranial dysostosis is a general skeletal condition [8] so named from the collarbone (cleido-) and cranium deformities which people with it often have.

People with the condition usually present with a painless swelling in the area of the clavicles at 2–3 years of age. [9] Common features are:

Other features are: parietal bossing, basilar invagination (atlantoaxial impaction), persistent metopic suture, abnormal ear structures with hearing loss, supernumerary ribs, hemivertebrae with spondylosis, small and high scapulae, hypoplasia of illiac bones, absence of the pubic bone, short / absent fibular bones, short / absent radial bones, hypoplastic terminal phalanges. [17]

Genetics

CCD is usually autosomal dominant, but in some cases its cause is not known. [18] The main mechanism is thought to involve haploinsufficiency caused by mutations in CBFA1 (also known as Runx2), a gene located on the short arm of chromosome 6 (6p21), which encodes a transcription factor required for the differentiation of stem cells into osteoblasts. [10] This results in delayed ossification of midline structures of the body and ensuing defects in membranous and endochondral bone formation. [19]

Diagnosis

Different features of the dysostosis are significant. Radiological imaging helps confirm the diagnosis. During gestation (pregnancy), clavicular size can be calculated using available nomograms. Wormian bones can sometimes be observed in the skull. [20]

Diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or by the identification of a heterozygous pathogenic variant in RUNX2 (CBFA1). [21]

Treatment

Around 5 years of age, surgical correction may be necessary to prevent any worsening of the deformity. [9] If the mother has dysplasia, caesarian delivery may be necessary. Craniofacial surgery may be necessary to correct skull defects. [20] Coxa vara is treated by corrective femoral osteotomies. If there is brachial plexus irritation with pain and numbness, excision of the clavicular fragments can be performed to decompress it. [10] In case of open fontanelle, appropriate headgear may be advised by the orthopedist for protection from injury.[ citation needed ]

Prognosis

Several studies have reported that life expectancy appears to be normal for people with CCD. [3] [22] [23]

Epidemiology

Cleidocranial dysostosis affects about one per million people. [1]

Notable cases

In 1987, a young girl named Jessica McClure fell down a narrow well pipe in her family's Texas property. Ron Short, a roofing contractor who was born without collarbones because of cleidocranial dysostosis and thus could collapse his shoulders to work in cramped corners, arrived at the site and offered to go down the shaft. The rescuers did not end up using him, [24] [25] though McClure was successfully recovered from the well.

Actor Gaten Matarazzo was born with cleidocranial dysplasia, which is incorporated into his character Dustin Henderson's storyline on Stranger Things . [26]

Sibling actress-singers Milly [27] and Abby Shapiro were born with cleidocranial dysplasia, a trait they share with their mother. [28]

Related Research Articles

CCD may refer to:

<span class="mw-page-title-main">Clavicle</span> Long bone that serves as a strut between the scapula and the sternum

The clavicle, or collarbone, is a slender, S-shaped long bone approximately 6 inches (15 cm) long that serves as a strut between the shoulder blade and the sternum (breastbone). There are two clavicles, one on the left and one on the right. The clavicle is the only long bone in the body that lies horizontally. Together with the shoulder blade, it makes up the shoulder girdle. It is a palpable bone and, in people who have less fat in this region, the location of the bone is clearly visible. It receives its name from Latin clavicula 'little key' because the bone rotates along its axis like a key when the shoulder is abducted. The clavicle is the most commonly fractured bone. It can easily be fractured by impacts to the shoulder from the force of falling on outstretched arms or by a direct hit.

<span class="mw-page-title-main">Fontanelle</span> Anatomical feature of the infant human skull

A fontanelle is an anatomical feature of the infant human skull comprising soft membranous gaps (sutures) between the cranial bones that make up the calvaria of a fetus or an infant. Fontanelles allow for stretching and deformation of the neurocranium both during birth and later as the brain expands faster than the surrounding bone can grow. Premature complete ossification of the sutures is called craniosynostosis.

<span class="mw-page-title-main">Macrocephaly</span> Abnormally large head size

Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to determine whether the syndrome is accompanied by particular disorders. Those with benign or familial macrocephaly are considered to have megalencephaly.

<span class="mw-page-title-main">Brachycephaly</span> Short, broad head

Brachycephaly is the shape of a skull shorter than average in its species. It is perceived as a cosmetically desirable trait in some domesticated dog and cat breeds, notably the pug and Persian, and can be normal or abnormal in other animal species.

<span class="mw-page-title-main">Hyperdontia</span> Condition of having extra teeth beyond the regular number of teeth

Hyperdontia is the condition of having supernumerary teeth, or teeth that appear in addition to the regular number of teeth. They can appear in any area of the dental arch and can affect any dental organ. The opposite of hyperdontia is hypodontia, where there is a congenital lack of teeth, which is a condition seen more commonly than hyperdontia. The scientific definition of hyperdontia is "any tooth or odontogenic structure that is formed from tooth germ in excess of usual number for any given region of the dental arch." The additional teeth, which may be few or many, can occur on any place in the dental arch. Their arrangement may be symmetrical or non-symmetrical.

<span class="mw-page-title-main">Ellis–Van Creveld syndrome</span> Medical condition

Ellis–Van Creveld syndrome is a rare genetic disorder of the skeletal dysplasia type.

An osteochondrodysplasia, or skeletal dysplasia, is a disorder of the development of bone and cartilage. Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Nonetheless, if taken collectively, genetic skeletal dysplasias or osteochondrodysplasias comprise a recognizable group of genetically determined disorders with generalized skeletal affection. These disorders lead to disproportionate short stature and bone abnormalities, particularly in the arms, legs, and spine. Skeletal dysplasia can result in marked functional limitation and even mortality.

Amastia refers to a rare clinical anomaly in which both internal breast tissue and the visible nipple are absent on one or both sides. It affects both men and women. Amastia can be either isolated or comorbid with other syndromes, such as ectodermal dysplasia, Syndactyly and lipoatrophic diabetes. This abnormality can be classified into various types, and each could result from different pathologies. Amastia differs from amazia and athelia. Amazia is the absence of one or both mammary glands but the nipples remain present, and athelia is the absence of one or both nipples, but the mammary gland remains.

<span class="mw-page-title-main">RUNX2</span> Protein-coding gene in humans

Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the RUNX2 gene. RUNX2 is a key transcription factor associated with osteoblast differentiation.

Metaphyseal dysplasia, or Pyle disease, is a disorder of the bones. It is a rare disease in which the outer part of the shafts of long bones is thinner than normal and there is an increased chance of fractures. Its hallmark feature is an abnormality of the long bones in the arms and legs in which the ends (metaphyses) of the bones are abnormally broad; the shape of the bones resembles a boat oar or paddle. The broad metaphyses are due to enlargement of the spongy inner layer of bone. Although trabecular bone is expanded, the dense outermost layer of bone is thinner than normal. As a result, the bones are fragile and fracture easily. The bone abnormalities in the legs commonly cause knock knees in affected individuals.

<span class="mw-page-title-main">Tooth eruption</span> Process in tooth development

Tooth eruption is a process in tooth development in which the teeth enter the mouth and become visible. It is currently believed that the periodontal ligament plays an important role in tooth eruption. The first human teeth to appear, the deciduous (primary) teeth, erupt into the mouth from around 6 months until 2 years of age, in a process known as "teething". These teeth are the only ones in the mouth until a person is about 6 years old creating the primary dentition stage. At that time, the first permanent tooth erupts and begins a time in which there is a combination of primary and permanent teeth, known as the mixed dentition stage, which lasts until the last primary tooth is lost. Then, the remaining permanent teeth erupt into the mouth during the permanent dentition stage.

Acrodysostosis is a rare congenital malformation syndrome which involves shortening of the interphalangeal joints of the hands and feet, intellectual disability in approximately 90% of affected children, and peculiar facies. Other common abnormalities include short head, small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.

<span class="mw-page-title-main">Pycnodysostosis</span> Genetic disease

Pycnodysostosis, is a lysosomal storage disease of the bone caused by a mutation in the gene that codes the enzyme cathepsin K. It is also known as PKND and PYCD.

<span class="mw-page-title-main">Frontonasal dysplasia</span> Medical condition

Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism, a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

3-M syndrome or 3M3 is a rare hereditary disorder characterized by severe growth retardation, facial dysmorphia, and skeletal abnormalities. The name 3-M is derived from the initials of the three researchers who first identified it: Miller, McKusick, and Malvaux and report their findings in the medical literature in 1972. Mutations in any one of the following three genes: CUL7, OBSL1, and CCDC8 are responsible for the occurrence of this disorder. It is inherited through an autosomal recessive pattern and considered very rare, so far less than 100 cases worldwide have been identified. Diagnosis is based on the presence of clinical features. Genetic testing can confirm the diagnosis and identify the specific gene involved. Treatment is aimed at addressing the growth and skeletal problems and may include surgical bone lengthening, adaptive aids, and physical therapy. An endocrinologist may assist with growth hormone replacement and appropriate evaluations during puberty.

<span class="mw-page-title-main">Hanhart syndrome</span> Class of congenital medical conditions

Hanhart syndrome is a broadly classified medical condition consisting of congenital disorders that cause an undeveloped tongue and malformed extremities and fingers. There exist five types of Hanhart syndrome, with the severity and nature of the condition ranging widely on a case-by-case basis. Hanhart syndrome is classified as a rare disease, with approximately 30 known cases having been reported between 1932 and 1991. Early hypotheses believed that the disorder was caused by genetic conditions, with a more recent hypothesis demonstrating that the disorder may be caused by hemorrhagic lesions during prenatal development. The causal mechanism behind this vascular disruption is still unknown.

<span class="mw-page-title-main">Skull bossing</span> Protrusion of the bones of the skull, typically the forehead

Skull bossing is a descriptive term in medical physical examination indicating a protuberance of the skull, most often in the frontal bones of the forehead. Although prominence of the skull bones may be normal, skull bossing may be associated with certain medical conditions, including nutritional, metabolic, hormonal, and hematologic disorders.

<span class="mw-page-title-main">Calvarial doughnut lesions-bone fragility syndrome</span> Medical condition

Calvarial doughnut lesions-bone fragility syndrome, also known as familial calvarial doughnut lesions, is a rare autosomal dominant genetic disorder characterized by mild to moderate fragility of the bones accompanied with calvarial doughnut lesions.

The Crane–Heise syndrome is a very rare and lethal birth defect without a known cause. It was first described in a 1981 publication, and its main signs are facial malformations, lack of bone mineralization, and musculoskeletal anomalies.

References

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  2. ↑ Rare Genetic Disorders That Affect the Skeleton. AuthorHouse. 2013. p. 43. ISBN   9781491815045. Archived from the original on 2017-11-05.
  3. 1 2 3 4 Young, Ian D. (2002). Genetics for Orthopedic Surgeons: The Molecular Genetic Basis of Orthopedic Disorders. Remedica. p. 92. ISBN   9781901346428. Archived from the original on 2016-11-03.
  4. 1 2 3 "Cleidocranial dysplasia". rarediseases.info.nih.gov. Genetic and Rare Diseases Information Center. 2016. Archived from the original on 28 January 2017. Retrieved 29 October 2017.
  5. 1 2 3 4 5 "Cleidocranial Dysplasia". rarediseases.org. National Organization for Rare Disorders, Inc. 2004. Archived from the original on 3 October 2016. Retrieved 2 October 2016.
  6. ↑ Epstein, Charles J.; Erickson, Robert P.; Wynshaw-Boris, Anthony Joseph (2004). Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. Oxford University Press. p. 333. ISBN   9780195145021. Archived from the original on 2016-10-03.
  7. ↑ "Cleidocranial Dysostosis". UCSF Benioff Children's Hospital. Archived from the original on 29 October 2016. Retrieved 2 October 2016.
  8. ↑ Garg RK, Agrawal P (2008). "Clinical spectrum of cleidocranial dysplasia: a case report". Cases J. 1 (1): 377. doi: 10.1186/1757-1626-1-377 . PMC   2614945 . PMID   19063717.
  9. 1 2 Hefti, Fritz (2007). Pediatric Orthopedics in Practice. Springer. p. 478. ISBN   9783540699644.
  10. 1 2 3 4 5 Turek's Orthopaedics: Principles And Their Application. Lippincott Williams & Wilkins. 2005. pp. 251–252. ISBN   9780781742986.
  11. 1 2 Juhl, John (1998). Paul and Juhl's essentials of radiologic imaging (7th ed.). Lippincott-Raven. ISBN   9780397584215.
  12. ↑ Greene, Walter (2006). Netter's Orthopaedics (1st ed.). Masson. ISBN   9781929007028.
  13. ↑ Textbook of Radiology and Imaging: Volume 2, 7e. Elsevier Science Health Science Division. 2003. p. 1539. ISBN   9780443071096.
  14. 1 2 Vanderwerf, Sally (1998). Elsevier's medical terminology for the practicing nurse. Elsevier. p. 65. ISBN   9780444824707.
  15. ↑ Menkes, John (2006). Child Neurology, 7e. Lippincott Williams & Wilkins. p. 307. ISBN   9780781751049.
  16. ↑ "Cleidocranial dysostosis". Mount Sinai Health System. Retrieved 30 January 2023.
  17. ↑ "Cleidocranial dysostosis". Radiopaedia.org. Archived from the original on 2015-06-26. Retrieved 2015-06-26.
  18. ↑ Tanaka JL, Ono E, Filho EM, Castilho JC, Moraes LC, Moraes ME (September 2006). "Cleidocranial dysplasia: importance of radiographic images in diagnosis of the condition". J Oral Sci. 48 (3): 161–6. doi: 10.2334/josnusd.48.161 . hdl: 11449/69073 . PMID   17023750.
  19. ↑ Saraswathivilasam S. Suresh, A Family With Cleidocranial Dysplasia And Crossed Ectopic Kidney In One Child, Acta Orthop. Belg. 2009, N° 4 (Vol. 75/4) p.521-527. "A family with cleidocranial dysplasia and crossed ectopic kidney in one child". Archived from the original on 2015-06-26. Retrieved 2015-06-26.
  20. 1 2 Lovell, Wood (2006). Lovell & Winter's Pediatric Orthopaedics, 6e. Lippincott Williams & Wilkins. p. 240. ISBN   9780781753586.
  21. ↑ Machol, Keren; et al. (November 16, 2017). "Cleidocranial Dysplasia Spectrum Disorder". GeneReviews. PMID   20301686.
  22. ↑ Dore; et al. (January 1987). "Cleidocranial Dysostosis and Syringomyelia Review of the Literature and Case Report". Clinical Orthopaedics & Related Research. January 1987 (214): 229–34. PMID   3791747. Archived from the original on 2016-11-03.
  23. ↑ Nebgen, Denise; Wood, Robert S.; Shapiro, Robert D. (1991). "Management of a mandibular fracture in a patient with cleidocranial dysplasia: Report of a case and review of the literature". Journal of Oral and Maxillofacial Surgery. 49 (4): 405–409. doi:10.1016/0278-2391(91)90380-5. PMID   2005496.
  24. ↑ Kennedy, J. Michael (1987-10-17). "Jessica Makes It to Safety—After 58 1/2 Hours". Los Angeles Times. Archived from the original on 2010-06-19.
  25. ↑ Scott, Ronald W. (November 1988). "Cleidocranial Dysplasia - An Enigma Among Anomalies". Journal of Orthopaedic & Sports Physical Therapy. 10 (5): 184–188. doi: 10.2519/jospt.1988.10.5.184 . PMID   18796963.
  26. ↑ Oyla, Gabrielle (2016-09-12). "Stranger Things' Gaten Matarazzo Discusses Living with Cleidocranial Dysplasia". People.com. Archived from the original on 2016-09-16.
  27. ↑ Shapiro, Milly (7 March 2019). "It was such an honor to attend the CCD Smiles event this past weekend. It was really powerful to be in a room full of other people with CCD..." Instagram . Archived from the original on 2021-12-23. Retrieved 15 June 2020.
  28. ↑ Starr, Michael (11 June 2020). "Meet new 'Doom Patrol' co-star Abigail Shapiro". New York Post . Retrieved 15 June 2020.
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