Cerebrocostomandibular syndrome is an extremely rare inherited disorder characterized by an abnormally small jaw (micrognathia), malformations of the roof of the mouth (palate), improper positioning of the tongue (glossoptosis), and abnormal development of the ribs (rib dysplasia). In most cases, such abnormalities contribute to respiratory problems (insufficiency) during early infancy. Although some affected individuals have normal intelligence, others exhibit moderate to severe mental retardation. Although research suggests that cerebrocostomandibular syndrome is usually inherited as an autosomal recessive genetic trait, some cases have also been documented in the medical literature that suggest autosomal dominant inheritance.
Cerebrocostomandibular syndrome is an extremely rare inherited disorder that is primarily characterized by abnormalities of the jaw, the roof of the mouth (palate), and the ribs, potentially contributing to respiratory difficulties during early infancy.
Most affected individuals exhibit abnormally slow growth during fetal development (intrauterine growth retardation) and after birth (postnatal growth deficiency). In addition, most infants with cerebrocostomandibular syndrome exhibit characteristic malformations of the head and facial (craniofacial) area. These may include underdevelopment of the jaw bones (micrognathia); malformations of the roof of the mouth (palate) such as incomplete closure of the palate (cleft palate); and/or an abnormally “drawn back” (retracted) or downwardly positioned tongue (glossoptosis). (The association of micrognathia, glossoptosis, and cleft palate may be referred to as “Pierre Robin anomaly.” [For more information, see the Related Disorders section below.]) In approximately one third of cases, affected infants may also have an abnormally small head (microcephaly).
In addition, in most cases, affected infants exhibit improper development of the ribs (rib dysplasia). Abnormal “gaps” may be present in the back (posterior) portions of the ribs near the spinal column (paravertebral portions) due to the abnormal replacement of bone with fibrous connective tissue. Such abnormal gaps may be present in all or some of the ribs. However, in most cases, the fourth to the seventh pairs of ribs tend to be involved, while the lower ribs tend not to exhibit such gaps. (There are normally 12 pairs of ribs.) Ribs on both sides of the body are affected (bilateral), although the distribution of the gaps may be uneven (asymmetric). As affected individuals age, the abnormal gaps are eventually joined by bony “bridges.” In some cases, additional rib (costal) abnormalities may also be present. The lower pairs of ribs may be incompletely developed (rudimentary) and, in approximately half of affected individuals, the twelfth (lowest) pair of ribs may be absent.
In infants with cerebrocostomandibular syndrome, such rib dysplasia may cause the upper chest to appear abnormally small, flat, and narrow; result in instability in portions of the chest wall; and contribute to abnormal breathing rhythms characterized by inward movement (contraction) of portions of the chest wall during inhalation (inspiration) and bulging of the chest wall during exhalation (flail chest, i.e., the opposite of normal breathing patterns).
In affected individuals, abnormalities of the jaw, palate, and ribs may contribute to respiratory difficulties during early infancy resulting in rapid, shallow breathing and inadequate levels of circulating oxygen (neonatal hypoxia). Affected infants may also be especially prone to repeated respiratory infections. Such respiratory abnormalities may potentially result in life-threatening symptoms.
In addition, approximately one third of individuals with cerebrocostomandibular syndrome exhibit moderate to severe mental retardation.
Due to severe underdevelopment of the jaws (micrognathia), malformations of the roof of the mouth (palate), and/or other associated abnormalities, many infants with Cerebrocostomandibular syndrome may also experience feeding difficulties and fail to gain weight at the expected rate (failure to thrive).
In some cases, affected individuals may also exhibit additional physical abnormalities such as improper development of bone and/or cartilage of the windpipe (trachea), elbows, and/or hips; webbing of the neck (pterygium colli); hearing loss due to improper conduction of sound from the outer or middle ear to the inner ear (conductive hearing loss); and/or speech impairment.
Most cases of cerebrocostomandibular syndrome that have been reported in the medical literature have appeared to occur randomly, for no apparent reason (sporadic). In such cases, no familial history of the disease has been apparent.
Research suggests that, in some families, cerebrocostomandibular syndrome is inherited as an autosomal recessive genetic trait with high penetrance. (“High penetrance” indicates that the characteristics associated with the disorder tend to be manifested in most of those who inherit the gene.) In other families, it appears to be inherited as an autosomal dominant trait.
Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
Cerebrocostomandibular syndrome is a very rare disorder that is apparent at birth (congenital). The disorder appears to affect males and females in equal numbers. Approximately 50 cases have been reported in the medical literature.
In some cases, cerebrocostomandibular syndrome may be diagnosed before birth (prenatally) through the use of advanced imaging techniques such as ultrasound. In fetal ultrasonography, reflected sound waves may be used to create an image of the developing fetus, revealing characteristic findings suggestive of cerebrocostomandibular syndrome (e.g., short, improperly developed ribs; abnormal smallness of the jaw; etc.).
In most cases, cerebrocostomandibular syndrome is diagnosed and/or confirmed after birth (postnatally) based upon a thorough clinical evaluation, identification of characteristic physical findings, and imaging tests. For example, x-ray studies may confirm and/or reveal the extent of micrognathia, rib (costal) malformations, and/or any associated abnormalities.
The treatment of cerebrocostomandibular syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who diagnose and treat abnormalities of the lungs (pulmonologists), specialists who assess and treat hearing problems (audiologists), speech pathologists, and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
Specific therapies for the treatment of cerebrocostomandibular syndrome are symptomatic and supportive. Because infants with the disorder may be prone to respiratory difficulty as well as repeated respiratory infections, physicians may closely monitor affected infants, recommend preventive measures, and, in cases of respiratory infections, may institute immediate antibiotic therapy and/or other steps to promptly, aggressively treat such infections. In cases of severe respiratory difficulty during early infancy, an incision may be made into the windpipe (trachea) to create a temporary opening that will allow the intake of air (tracheostomy). In addition, special supportive therapies may be provided to help ensure appropriate nutritional intake in infants who also experience feeding problems.
The Vertical Expandable Prosthetic Titanium Rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. The titanium rib was developed at the University of Texas Health Science Center in San Antonio. It is manufactured by Synthes Spine Co.. http://www.synthes.com/sites/NA/Products/Spine/Screw_Hook_Rod_and_Clamp_System/Pages/VEPTR_and_VEPTR_II.aspx
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In some cases, surgery may be performed to correct and/or reconstruct certain craniofacial malformations such as cleft palate. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.
If individuals with cerebrocostomandibular syndrome exhibit conductive hearing loss, the use of hearing aids may be beneficial. In addition, early intervention is important to ensure that affected children reach their potential. Special services that may be beneficial may include special education, speech therapy, and other medical, social, and/or vocational services.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 7/1/96. Entry Number 117650.