Cerebro-costo-mandibular syndrome is a very rare genetic disorder in which mutations in the small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) genes cause various skeletal anomalies of the thorax and spine. The diagnosis is made based on clinical criteria and the prognosis depends on the severity of defects and associated complications, most important being frequent upper respiratory tract infections.
Cerebro-Costo-Mandibular syndrome (CCMS) is presumably inherited through an autosomal dominant mode (although sporadic cases have been identified). This means that symptoms are almost universally seen in the setting of a positive family history. They can commence soon after birth, but the majority of cases are diagnosed during infancy or childhood  . The cardinal features of CCMS are:
- Facial changes - Normal development of the palate may be impaired due to insufficient growth of the mandible during fetal life, leading to an abnormally positioned tongue and an underdeveloped mandible (known as micrognathia) that is evident on physical examination  . Furthermore, a cleft palate and feeding difficulties are frequently noted , and the term "Pierre Robin sequence" is frequently used to describe facial and mandibular features seen in this syndrome .
- Defects of the thorax and spine - "rib-gap syndrome" is a synonym for CCMS, the primary reason being the appearance of bilateral multiple posterior rib gaps (most frequently between the 4th and 10th ribs) that are often misidentified as rib fractures   . As a result, pulmonary function is significantly reduced. Together with scoliosis and laryngotracheal abnormalities and other prominent findings in CCMS patients, they predispose to profound respiratory obstruction and frequent respiratory tract infections. They are the most important cause of early death. Mortality rates range from 35-50% in the first year of life in the absence of the correct diagnosis and proper management  . Blockade of the nasal passage (choanal atresia) may also be encountered, further contributing to the respiratory pathology .
- Cranial abnormalities - A very small head circumference with severe microcephaly, as well as mental retardation, is observed in a minority of patients, with the extent of brain damage depending on the time of diagnosis   .
- Miscellaneous findings - Congenital heart disease (septal defects), a horseshoe kidney, hearing loss, hypoplasia of the elbows and the clavicle and hypospadias are other notable findings in CCMS  .
Entire Body System
Cerebro-costo-mandibular syndrome is a rare disorder characterized by psychomotor retardation, posterior rib-gap defects, and the orofacial defects of Pierre Robin sequence. [ncbi.nlm.nih.gov]
Psychomotor retardation, which hasbeen described in almost one-half of CCMS cases, is anothercontroversial nding of CCMS.1 It is thought to be the resultof perinatal and postnatal hypoxia, although cerebralndings of the reported cases do not support this [documents.tips]
Psychomotor retardation, which has been described in almost one-half of CCMS cases, is another controversial ﬁnding of CCMS.1 It is thought to be the result of perinatal and postnatal hypoxia, although cerebral ﬁndings of the reported cases do not support [datospdf.com]
This may support the hypothesis that psychomotor retardation is most likely secondary induced. Meineke et al.  suggested al- ready that costo-mandibular syndrome might be a bet- ter designation than CCMS. [docslide.com.br]
The diagnosis of CCMS may not be easy, as less than 100 cases have been described in the literature  . Nevertheless, a detailed patient history regarding the onset of symptoms and a thorough physical examination can provide sufficient data to raise clinical suspicion. The presence of micrognathia and respiratory difficulties necessitate the use of imaging studies, such as plain radiography, computed tomography (CT) or magnetic resonance imaging (MRI). Chest X-rays will reveal a narrow or bell-shaped thorax and bilateral multiple posterior rib gaps, while mandibular hypoplasia can be confirmed using either X-rays or CT   . Radiography may be employed if hypoplasia of other skeletal structures (extremities or the clavicles) is suspected as well, whereas cardiac and renal structures should be evaluated by CT or MRI. Additionally, endocranial imaging (preferably MRI) is advocated, particularly if signs of mental retardation exist . Some reports suggest that a prenatal diagnosis of CCMS can be made using fetal ultrasonography and identifying thoracic, facial abnormalities and increased nuchal translucency .
- Tooley M, Lynch D, Bernier F, Parboosingh J, Bhoj E, Zackai E, et al. Cerebro-costo-mandibular syndrome: Clinical, radiological, and genetic findings. Am J Med Genet A. 2016;170A(5):1115-1126.
- Abdalla W, Panigrahy A, Bartoletti SC. Cerebro-costo-mandibular syndrome: Report of two cases. Radiol Case Rep. 2011;6(3):495.
- Watson TA, Arthurs OJ, Muthialu N, Calder AD. Multi-detector thoracic CT findings in cerebro-costo-mandibular syndrome: rib gaps and failure of costo-vertebral separation. Skeletal Radiol. 2014;43(2):263-266.
- Nagasawa H, Yamamoto Y, Kohno Y. Cerebro-costo-mandibular syndrome: prognosis and proposal for classification. Congenit Anom (Kyoto). 2010;50(3):171-174.
- Ramaswamy P, Negus S, Homfray T, De Rooy L. Severe micrognathia with rib dysplasia: cerebro-costo-mandibular syndrome. Arch Dis Child Fetal Neonatal Ed. 2016;101(1):F85.
- Hosalkar HS, Shaw BA, Ceppi CL, Ng BC. The cerebro-costo-mandibular syndrome: 9-year follow-up of a case. J Postgrad Med. 2000;46:268.