Intro

 Also known as marie & sainton’s disease,scheuthaner-marie-saniton syndrome,mutational dystosis.

cleido meaning collarbone, cranial from the Greek κρανιὀς meaning skull, and dysostosis meaning
formation of abnormal bone. Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia
representing a clinical continuum ranging from triad of delayed closure of the cranial sutures,
hypoplastic or aplastic clavicles, and dental abnormalities) ……. At birth, affected individuals typically
have abnormally large, wide-open fontanelles that may remain open throughout life. Clavicular
hypoplasia can result in narrow, sloping shoulders that can be opposed at the midline. Moderate short
stature may be observed, with most affected individuals being shorter than their unaffected sibs. Dental
anomalies may include supernumerary teeth, eruption failure of the permanent teeth, and presence of
the second permanent molar with the primary dentition…

Skeletal Dysplasia

Skeletal dysplasia is an umbrella term which refers to diseases of bones characteristics by abnormal
shape, size, growth and density of bone. It is a group of more than 450 heritable disorders. While it
mainly effects bones and cartilage, it can also have significant effects on muscle, tendons and ligaments.
The type of skeletal dysplasia depends on which parts of the skeleton are involved .

Warman ML, Cormier-Daire V, Hall C, et al. Nosology and classification of genetic skeletal disorders:
2010 revision. American journal of medical genetics. Part A. 2011 May;155A(5):943–968

One such skeletal dysplasia is cleidocranial dysplasia in which deformities are found mainly in the skull
and collar bone.

While skeletal dysplasias are inherited in an autosomal recessive, autosomal dominant, X-linked
recessive, X-linked dominant and Y-linked manner. Cleidocranial dysplasia in specific is caused by
autosomal dominant allele of mutated CBF1 gene

Clinical feature

 Abnormally large, wide-open fontanelles at birth that may remain open throughout

life. The wide-open metopic suture results in separation of the frontal bones by a metopic
groove. The forehead is broad and flat; the cranium is brachycephalic.
 Frontal and parietal bossing and mid-face retrusion
 Paranasal sinuses are underdeveloped and narrow.
 Narrow, sloping shoulders that can be opposed at the midline due to clavicular
hypoplasia or aplasia (see Figure 1)
  Defect of shoulder girdle ranges from absence of clavicle about in 10% of cases, to partial
absence or even thinning of one or both clavicles
  Abnormal dentition including delayed eruption of secondary dentition, failure to shed
the primary teeth, variable numbers of supernumerary teeth along with dental crowding,
and malocclusion
 Hand abnormalities including brachydactyly, tapering fingers, and short, broad thumbs
 Short stature (typically moderate)
 Normal intellect in individuals with classic CCD spectrum disorder
 Hypertelorism – wide nasal bridge due to increased space between the eyes

Dental abnormalities

Dental abnormalities seen in cleidocranial dysplasia may include:  Delayed loss of the primary
teeth 

Delayed appearance of the secondary teeth  Unusually shaped, peg-like teeth

 Misalignment of the teeth and jaws (malocclusion)

Thinner root of teeth

 Supernumerary teeth, sometimes accompanied by cysts in the gums.

Maxilla & paranasal sinuses are underdeveloped resulting in maxillary macrognathia.  Complete
absence of cementum

oots of teeth are often short and thinner than normal.

 Crown may be pilled as a result of enamel hypoplasia.

https://www.ncbi.nlm.nih.gov/books/NBK1513/

Epidemiology
CCD spectrum disorder is present at a frequency of one in 1,000,000 individuals worldwide. It affects
all ethnic groups. Males and females are equally commonly affected.
https://www.ncbi.nlm.nih.gov/books/NBK1513/ Males and females are equally commonly affected

Signs and symptoms

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

1.Partly and at times completely missing clavicle or clavicle reduced to small vestiges. This results
into hypermobility of shoulders allowing them to together in front of the chest.

Soft spot at the top of the head where fontanelle failed to close

Hyperdontia that is supernumerary teeth.

Bossing of forehead

Hypertelorism
Pathophysiology/Etiology
It is familial and appears as true dominant mendelian characteristic.  Mutations in the core binding
factor alpha 1 (CBFA) gene located on chromosome 6p21 is the cause of cleidocranial dysplasia.

t is usually autosomal dominant, but in some cases the cause is not known.[17] It occurs due
to haploinsufficiency caused by mutations in the CBFA1 gene (also called Runx2), located on the
short arm of chromosome 6, which encodes transcription factor required
for osteoblast differentiation.[10] It results in delayed ossification of midline structures of the body,
particularly membranous bone.
A new article reports that the CCD cause is thought to be due to a CBFA1 (core binding factor
activity 1) gene defect on the short arm of chromosome 6p21 . CBFA1 is vital
for differentiation of stem cells into osteoblasts, so any defect in this gene will cause defects
in membranous and endochondral bone formation.[18]
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.

It is a benign hereditary condition inherited as autosomal dominant disorder but upto 30% of cases
are due to spontaneous mutation.

If the mother has dysplasia, caesarian delivery may be necessary.

Diagnosis
Radiological imaging can be used diagnose clavicular size, skull and other bone deformation
As this disease is caused by mutations in the CBFA1 gene (also called Runx2) in chromosome 6,
this can be disgn

Diagnosis/testing.
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).

Treatment

There is no specific treatment for cleidocranial dysplasia, but certain procedures can be
performed-
 1.Irritation and numbness of brachial plexus (network of nerves extends from the spinal
cord over the first rib into the armpit) should be treated by excision of the clavicular
fragments by decompress it.
 Surgical correction may be necessary at 5 years of age to prevent any worsening of
condition.
 Craniofacial surgery is carried out to correct any defect of the skull.
 Dental treatments like applying dentures over unerupted teeth, teeth removal and
using prosthetic replacements speech therapy Lovell, Wood (2006). Lovell & Winter's Pediatric
Orthopaedics, 6e. Lippincott Williams & Wilkins
 In case of open fontanelle, appropriate headgear may be advised by the orthopedist for
protection from injury.
 Babies born with open frontanelle are given to wear headgear to protect them from injury
 Individuals may consider correction of the depressed forehead or lengthening of the hypoplastic
clavicles .
 If bone density is below normal on DXA, calcium and vitamin D supplementation are prescribed.