Bangalore, India

Synonyms: Rib gap defects with micrognathia[1]

Definition:  Cerebrocostomandibular syndrome is a potentially lethal developmental disorder characterized by mental handicap, palatal defects, micrognathia, and severe costovertebral defects[2].

History: The condition was first described in a female and 2 male sibs, by McNicholl et al[3].The affected children born to a normal father and mother were described to have a syndrome of mental retardation, palatal defects (short hard palate with central hole, absent soft palate, absent uvula), micrognathia, glossoptosis, and severe costovertebral abnormalities.

Prevalence: Less than 50 cases reported so far. M=F

Etiology:  The majority of cases are sporadic. Both autosomal dominant[4] and autosomal recessive inheritance[5] have been suggested. The suspected mechanism is an abnormal function of a gene or genes involved in rib chondrogenesis[6]. Myogenic factor-5, goosecoid, and CBFA1 have been proposed as candidate genes, on the basis of their role in bone formation[7].

Pathogenesis: A disorder of cellular growth and bone formation leading to diffuse midline mesenchymal tissue abnormalities.

Sonographic findings: The most prominent ultrasonographic sign is the unusual shape of the ribs, which are very short, defective or unossified. Rib lesions are bilateral but may not necessarily be symmetrical. Another important finding is the micrognathia and microcephaly[8]. Common findings are listed in the table below:

The following are images from Philip Ramm (AMS) (presented in Case 34).

Best "facial profile" obtainable. (The hand is incompletely visible but is normal). The image demonstrates the nose and upper lip. The lower lip and jaw are not in the same alignment, which strongly suggests micrognathia. This impression is reinforced by the generous amount of fluid in all images, compatible with a swallowing problem due to the micrognathia.

Several views of the spine at the thoracic and lumbar levels demonstrate nuchal thickening (yes i know that was easy...) but note also that the posterior elements of the spine are not visible. This can be due to an oblique section of course, or an anomaly. The image below labeled Section at the level of the abdomen clears the confusion and demonstrates that the soft-tissue behind the back are normal.

Section at the level of the abdomen.

The 2 last images have an incredibly obvious finding ... that is so difficult to find... Look carefully ! 

Yes.. where are the ribs ???

Associated anomalies: Other findings include:

·        Mental retardation in some patients, others may have normal intelligence.

·        Cartilage or bone may be abnormal in other areas such as trachea, hip and elbow.

·        The combination of micrognathia, glossoptosis and "flat chest†causes severe respiratory distress.

Complications: Respiratory distress, respiratory infection, failure to thrive, speech delay, hearing loss.

Differential diagnosis:
Ear, patella, short stature syndrome: also has slender ribs and micrognathia but the long bones are short. However, microtia is a distinguishing feature of the syndrome.

Campomelic dysplasia  In campomelic dysplasia the ribs are normally ossified but the fetus may be missing a pair of rib. The designation campomelic (or camptomelic) dwarfism, comes from the bowing of the legs, especially the tibias. The scapulas are very small and the pelvis and spine show changes. The inferior part of the scapula is hypoplastic. Cleft palate, micrognathia, flat face, and hypertelorism are also features. Most patients die in the neonatal period of respiratory distress.

Prognosis: Mortality in early infancy is high: 10 out of 24 cases, died before the age of 3 months. Yet, survival has extended to adulthood. All survivors showed growth disturbances^[9].

Recurrence risk:  Mendelian inheritance

Management:   Intensive care for respiratory distress, feeding difficulty and infection. Cleft palate repair, special education and hearing aids for hearing loss.

Reference

[1] Miller, K. E.; Allen, R. P.; Davis, W. S. Rib gap defects with micrognathia. Am. J. Roentgen. 114: 253-256, 1972.

[2] Kang YK, Lee SK, Chi JG.  Maxillo-mandibular development in cerebrocostomandibular syndrome. Pediatr Pathol. 1992 Sep-Oct;12(5):717-24.

[3] McNicholl, B.; Egan-Mitchell, B.; Murray, J. P.; Doyle, J. F.; Kennedy, J. D.; Crome, L. Cerebro-costo-mandibular syndrome: a new familial developmental disorder. Arch. Dis. Child. 45: 421-424, 1970.

[4] Leroy, J. G.; Devos, E. A.; Vanden Bulcke, L. J.; Robbe, N. S. Cerebro-costo-mandibular syndrome with autosomal dominant inheritance. J. Pediat. 99: 441-443, 1981.

[5] Silverman, F. N.; Strefling, A. M.; Stevenson, D. K.; Lazarus, J. Cerebro-costo-mandibular syndrome. J. Pediat. 97: 406-416, 1980.

[6] Kirk, E. P. E.; Arbuckle, S.; Ramm, P. L.; Ades, L. C. Severe micrognathia, cleft palate, absent olfactory tract, and abnormal rib development: cerebro-costo-mandibular syndrome or a new syndrome? Am. J. Med. Genet. 84: 120-124, 1999.

[7] R. Hennekam, R. C. M.; Goldschmeding. Complete absence of rib ossification, micrognathia and ear anomalies: extreme expression of cerebro-costo-mandibular syndrome? Europ. J. Hum. Genet. 6: 71-74, 1998.

[8] Merlob, P.; Schonfeld, A.; Grunebaum, A.; Mor, N.; Reisner, S. H. : Autosomal dominant cerebro-costo-mandibular syndrome: ultrasonographic and clinical findings. Am. J. Med. Genet. 26: 195-202, 1987.

[9] ML Buyse (Ed.) Cerebro-costo-mandibular syndrome  Birth defects  encyclopedia p.302