Cleidocranial dysplasia

Definition

Cleidocranial dysplasia (CCD), also known as cleidocranial dysostosis, is a hereditary condition characterized by abnormal clavicles, delayed fusion of the bones in the skull, extra teeth, short stature, and other skeletal changes.

Description

Cleidocranial dysplasia is one of the skeletal dysplasia conditions, a large family of disorders involving abnormal growth and development of the skeleton.

CCD involves a characteristic group of abnormalities affecting primarily the skull, teeth, and clavicles. Other bones, such as the ribs, pelvis, and bones of the hands and feet may also be affected. Older children and adults with CCD are typically shorter than average. Most individuals with this condition do not have significant physical or mental disability.

Genetic profile

CCD is an autosomal dominant condition with variable expressivity (variable symptoms) and complete penetrance (meaning that all individuals who carry the gene for CCD have some symptoms). It is estimated that one third of cases represent new mutations, or genetic changes. The gene responsible for CCD has been mapped to the short arm of chromosome 6 and is called CBFA1. This gene encodes a transcription factor, meaning a protein that regulates DNA transcription, and is specifically expressed in the bone. Mutations in CBFA1 have been identified in many individuals and families with CCD.

Demographics

More than 500 cases of CCD among individuals of various ethnic backgrounds have been described in the medical literature. The incidence of CCD is reported to be highest around Cape Town, South Africa. The number of affected individuals in this area was estimated to exceed 1,000 as of 1996. These individuals descended from an affected Chinese sailor who settled in the area in 1896 and had seven wives. Study of this large family helped localize the gene responsible for the condition.

Signs and symptoms

Individuals with CCD typically show a delay or failure of the fusion of the calvarial sutures, the openings between the bones of the skull in infants. In some cases, the anterior fontanelle (the "soft spot" on an infant's head) or other areas of the skull may remain unfused through life. A typical facial appearance in persons with CCD includes a broad forehead and widely spaced eyes. The overall head size is usually at the upper limit of normal.

Almost all persons with CCD have some degree of hypoplasia, or underdevelopment, of the clavicles (collar bones). In severe cases, both clavicles may be absent. More commonly, there is hypoplasia of the outside end of the clavicles. Depending on the degree of severity of clavicular hypoplasia, the external appearance of the shoulder may be affected. Some persons with CCD appear to have narrow, sloping shoulders, and some have the unusual ability to bring their shoulders together beneath their chin. This defect usually does not result in physical disability for the individual.

Dental abnormalities are very frequent among persons with CCD and are considered characteristic of the disorder. Almost all individuals are slow to lose their deciduous teeth (baby teeth), with a delay in the eruption of the permanent teeth. Some persons with CCD describe "living without teeth" until their permanent teeth started growing. Additionally, there may be a large number of extra teeth present. These extra teeth are so numerous so as to constitute a more or less complete third set of teeth. Additionally, the enamel of the teeth may be abnormal and prone to decay.

Other signs of CCD include a small rib cage with short or abnormal ribs. The vertebra of the spine may be malformed. The pelvis may be underdeveloped, with an increased space between the pubic bones. The growth of the bones in the hands and feet are often abnormal; most are shorter but others are longer than normal. Final height in adults with CCD is usually shorter than expected given the family background.

More unusual complications associated with CCD include scoliosis (curvature of the spine), bone fragility, deafness, cleft palate, and a small jaw.

Diagnosis

The diagnosis of CCD is typically made by the doctor following review of the information obtained from physical exams, history, and x ray or other studies. The clavicular hypoplasia may only be seen on x rays.

The combination of hypoplastic clavicles, open fontanelles, and extra teeth is considered typical of CCD. The multiple dental anomalies in CCD are also quite specific and the diagnosis is evident in any individual with normal deciduous teeth, delayed eruption of permanent teeth, and multiple extra teeth.

Testing of the CBFA1 gene for mutations may also be performed. Identification of a mutation may confirm the initial diagnosis, or allow diagnosis before birth.

In a few cases, recognition of the features of CCD by ultrasound imaging, a technique that produces pictures of the fetus, has led to diagnosis of the condition before birth.

Treatment and management

There is no specific treatment for cleidocranial dysplasia. Typically, a course of treatment is designed to manage the specific symptoms.

Children with CCD may be screened for deafness.

Long term dental treatment is often required. Surgery may be performed to remove the baby teeth and open the bony coverings surrounding the permanent teeth, with the goal of promoting their eruption. Orthodontic procedures may be required to align the teeth.

In pregnant females with CCD, the hypoplastic pelvis often necessitates a caesarian section delivery.

Prognosis

CCD is not expected to affect life expectancy in most cases and most diagnosed persons enjoy good over-all health.

In some newborns, the small rib cage and reduced lung capacity may lead to respiratory distress. Height is often lower compared to that of other family members. The clavicular hypoplasia does not appear to significantly impair function, and some individuals with hypoplastic or absent clavicles have worked as manual laborers without difficulty. Dental problems are expected, and are sometimes severe enough so as to become a "dental disability." Intelligence is usually normal.

Resources

BOOKS

Jones, K. L. Smith's Recognizable Patterns of Human Malformation. W. B. Saunders Company, Philadelphia, 1997.

PERIODICALS

Mundlos, S. "Cleidocranial Dysplasia: Clinical and Molecular Genetics." Journal of Medical Genetics 36 (1999):177-182.

Ramesar, Rajkumar S. et al. "Mapping the Gene for Cleidocranial Dysplasia in the historical Cape Town (Arnold) Kindred and Evidence for Locus Homogeneity." Journal of Medical Genetics 33 no. 6 (1996): 511-514.

Jennifer Roggenbuck, MS, CGC