A Guide to Cerebrocostomandibular Syndrome: A Comprehensive Overview of the Symptoms, Associated Genes, Tests, Treatment and Patient Support

Genetics, Science
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Symptoms and Description

Cerebrocostomandibular syndrome is a rare genetic disorder that presents with a typically small jaw, abnormal rib development and a small thorax combined with other abnormalities. It is a very rare genetic disorder which was first reported in 1966, and so far only 65 cases have been recorded and studied in the world.

These patients display a variety of rib malformations, deformities of the palate, micrognathia (very tiny jaw size), varying degrees of mental deficiency and severe cerebral under-development. The symptom range of rib defects vary from deformities in just three to four dorsal rib segments to complete absence of ossification.

In roughly 50 percent of the recorded cases so far, there is a high degree of cerebral involvement which invariably leads to mental retardation, microcephaly and histological abnormalities. The extreme type of rib malformations seen in cases of cerebrocostomandibular syndrome are never seen in any other disease, and this helps to a great extent in the primary diagnosis at birth.

The typical symptoms of cerebrocostomandibular syndrome also include defects of the palate in which the palate is short, hard and has a central hole, lack of soft palate and uvula, micrognathia, glossoptosis, and serious costovertebral abnormalities. A barking cough is also seen in patients who have tracheal cartilage abnormalities.

Other symptoms of cerebrocostomandibular syndrome include brain dysfunction, severe cerebral defects, vertebral abnormalities, subluxation of the elbows, dental defects, renal abnormalities, deformities of fingers and toes, deafness, hip dislocation and respiratory insufficiency.

What Causes Cerebrocostmandibular Syndrome: The Genetic Aspects

The incidence of cerebrocostmandibular syndrome is mostly sporadic but of recent, some recorded familial cases seem to suggest an autosomal recessive as well as an autosomal dominant method of inheritance.

In 2009, one research study on familial occurrences of cerebrocostomandibular syndrome successfully identified a homozygous splice site mutation in the COG1 gene as being responsible for the manifestation of disease. A homozygous G-to-A transition in intron 6 of the COG1 gene (location 1070+5G-A) causes the omission of exon 6, frameshift, and the occurrence of a prematurely truncated protein of 321 amino acids. RT-PCR analysis indicates only 3 percent of normal transcription as compared to healthy people. Thus, this is a mutation called a “leaky mutation”.

The mortality rate, especially in infants is a very high because of respiratory problems and the manifestation of ‘flail chest’. Most children born with this syndrome do not survive to attain the age of adulthood. Since there is as yet no confirmation of the mentioned mutations being common or the only cause of this disorder, the risk factors in families is difficult to assess. All the same, due to the genetic heterogeneity of this rare disease and the high degree of variability and expressivity, genetic counseling is a must if any case of Cerebrocostomandibular syndrome is diagnosed in a family.

Diagnosis, Treatment and Patient Management

The diagnosis of cerebrocostomandibular syndrome is usually confirmed by the use of thre factors; the X-ray examination of the ribcage, the presence of microganathia and the presence of some variation of cerebral dysfunction. Differential diagnosis is carried out with other syndromes like Robin’s anomalad or through defective rib development.

There is no known cure for cerebrocostomandibular syndrome and since many case studies have shown the prognosis to be bad, both for survival and intellectual capability, prospective parents must be prepared to face the possibility of immediate admission of the infant to the ICU (intensive care unit) right at delivery.

In addition, since intrauterine detection of cerebrocostomandibular syndrome is possible through sonography or ultrasound, the option of termination of the pregnancy should be taken, especially if the fetus shows severe micrognathia or serious costal maldevelopment. Management is applicable only if the thoracic development is enough and only a few ribs are affected with the presence of moderate micrognathia. In this case, intensive care at delivery helps to treat respiratory problems.

References

  1. Zeevaert, R. et al. (2009). Cerebrocostomandibular-like syndrome and a mutation in the conserved oligomeric Golgi complex, subunit 1. Hum. Molec. Genet. 18: 517-524, 2009.

  2. ‘MIM ID 117650 CEREBROCOSTOMANDIBULAR SYNDROME.’ (2010). Retrieved on November 18th, 2010 from OMIM (Online Medelian Inheritance in Man), NCBI (National Center for Biotechnology Information, U.S. National Library of Medicine):

https://www.ncbi.nlm.nih.gov/omim/117650

  1. Flodmark, P &, Wattsgård, C. (2001). Cerebro-costo-mandibular syndrome. Pediatr Radiol. 31(1):36-7.

  2. James, P. A. & Aftimos, S. (2003). Familial cerebro-costo-mandibular syndrome: a case with unusual prenatal findings and review. Clin. Dysmorph. 12: 63-68.