Cerebrocostomandibular syndrome (ORPHA:1393)
Cerebro-costo-mandibular syndrome (CCMS) is characterized at birth by posterior rib gaps and orofacial anomalies reminiscent of Pierre Robin syndrome (see this term) that include palatal defects (short hard palate, absent soft palate, absent uvula), micrognathia and glossoptosis.
Epidemiology
More than 80 cases have been reported to date; both males and females are equally affected.
Clinical description
CCMS is characterized by orofacial and costovertebral developmental anomalies. Severity is highly variable. Intrauterine growth retardation and low birth weights are common. Orofacial anomalies may include absent soft palate and a short hard palate with posterior notching, micrognathia and glossoptosis. Characteristic dorsal rib defects are sine qua non of the syndrome and often result in a bell-shaped thorax. Posterior rib gaps and rib defects are revealed by X-ray; there is no apparent continuity between the ossiﬁed ribs which are usually divided into two portions. This may lead to ''flail chest,'' a paradoxical movement of a segment of the thoracic wall due to broken ribs, which may further hamper respiration. Respiratory difficulties lead to generalized cyanosis and potential hypoxic brain injuries that may be responsible for intellectual deficit that may be observed later. Associated malformations were described in rare cases: microcephaly, absence of external ear canals and spina bifida. Those patients who survive infancy may suffer from growth retardation, scoliosis, reduced lung capacity, dental anomalies, feeding disturbances, conductive hearing loss and language disturbances. Patients who survive the first year of life are reported to survive to adulthood and to harbor a less severe form. These patients may suffer from growth retardation, scoliosis, reduced lung capacity, dentition anomalies, feeding disturbances, intellectual deficit, conductive hearing loss and language disturbance.
Etiology
No causative gene has been identified to date. It has been proposed, however, that defects in the sonic hedgehog (SHH) signaling cascade may be responsible for these developmental anomalies.
Diagnostic methods
Clinical presentation, along with typical chest X-ray findings, confirms the diagnosis.
Differential diagnosis
Differential diagnoses include trisomies 13 and 18, and Pierre Robin syndrome (see these terms).
Antenatal diagnosis
Although most cases are spontaneous, both autosomal recessive and autosomal dominant patterns of inheritance have been observed in familial cases.
Management and treatment
Orofacial anomalies responsible for breathing and feeding difficulties must be immediately addressed and severe cases must be transferred to intensive care units. Affected infants require feeding assistance and should lie in the prone position to help bring the tongue forward and liberate the trachea. Intubation or placement of a nasopharyngeal airway may be necessary. As tracheal intubation may prove impossible, a neonatal laryngeal mask airway, intermittently replaced by nasal prongs and continuous positive airway pressure, may be required. In these most severe cases, tongue-lip adhesion surgical intervention may provide a long term solution. A Haberman feeder may be of use in infants with cleft palate and nasogastric tube supplementation may be required to provide supplementary caloric intake.
Prognosis
Prognosis depends upon the severity of anomalies. The most severe forms are often fatal within the first hours after birth and 25% of all reported cases are fatal during the first month of life. This correlates significantly with greater numbers of missing ribs or gaps.

                            Last update: 
                            May 2013


                            - Expert reviewer(s): 
                            Dr Hiroyuki NAGASAWA