In 1966, Smith et al. described a rare disorder characterized mainly by growth retardation, dysmorphic chest, mandibular hypoplasia, glossoptosis and variable palatal abnormalities.
GENETICS/PATHOGENESIS
1. Inheritance
a. Sporadic in majority of cases
b. Familial occurrence in a few instances i. Autosomal recessive pattern ii. Autosomal dominant pattern 2. Pathogenesis of the rib gaps
a. Not well understood
b. Rib abnormality results from a lack of fusion between two mesenchymal tissues derived from the somatic mesoderm (posteriorly) and the lateral plate meso- derm (anteriorly)
c. Defective organization of the somite results in discon- tinuities of the ribs
CLINICAL FEATURES
1. Variable inter- and intra-familial expression 2. Cardinal signs
a. Rib abnormalities i. Posterior rib gaps
a) Present in almost all affected newborn infants b) Showing great variability in severity c) Disappear in time
d) Sometimes replaced by callus or pseudo- arthroses
ii. Segmentation defects and rudimentary rib devel- opment, fusion of most ribs to the vertebrae, and absence of any normal costovertebral articulations iii. Thin ribs
iv. Agenetic ribs
b. Micrognathia/Pierre Robin anomaly c. Cerebral abnormalities
i. Microcephaly
ii. Agenesis of the corpus callosum iii. Dilated lateral ventricles
iv. Porencephalic cyst
v. Variable degree of mental retardation probably sec- ondary to hypoxia following respiratory distress 3. Other skeletal anomalies
a. Vertebral anomalies including hemivertebrae b. Hip dislocation
c. Subluxation of the elbows d. Pectus carinatum
e. Hypoplasia of the sternum, clavicles, and pubic rami f. Epiphyseal stippling
g. Abnormal phalanges and toes h. Clubfoot
4. Intrauterine growth retardation
5. Postnatal growth deficiency 6. Respiratory distress 7. Feeding difficulties 8. Language delay 9. Conductive deafness 10. Palatal defect
a. Short soft palate b. Cleft palate 11. Dental defects
12. Laryngeal and tracheal abnormalities 13. Pterygium coli
14. Renal anomalies a. Renal cysts b. Ectopia
15. Congenital heart defects 16. Prognosis
a. Mental retardation often among the late survivors b. High mortality (40% in the first year of life, 50% in
the first month of life) mostly due to respiratory insuf- ficiency secondary to rib abnormalities and flail chest
DIAGNOSTIC INVESTIGATIONS
1. Radiography
a. Rib malformations
i. Multiple gaps consisting of fibrous or cartilagi- nous tissue
ii. Thin ribs iii. Agenetic ribs b. Vertebral anomalies
c. Other associated skeletal anomalies d. Micrognathia
2. Cranial ultrasonography for cerebral abnormalities 3. Histology of rib gaps: undifferentiated fibrous connective
tissue and muscles, instead of cartilage and bone
GENETIC COUNSELING
1. Recurrence risk a. Patient’s sib
i. Not increased in sporadic cases and in a fresh mutation case of an autosomal dominant disorder ii. 25% in an autosomal recessive disorder
b. Patient’s offspring: not increased unless the patient survives and is affected with an autosomal dominant disorder in which case there is a 50% risk of having an affected child
2. Prenatal diagnosis by ultrasonography: difficult to establish a. Small mandible
b. A narrow short chest c. Defective ribs d. Growth retardation e. Vertebral anomalies
f. Limb anomalies 139
Cerebro-Costo-Mandibular Syndrome
140 CEREBRO-COSTO-MANDIBULAR SYNDROME
g. Increased nuchal translucency h. Cystic hygroma
i. Polyhydramnios 3. Management
a. Treatment of respiratory distress b. Nasogastric tube feeding c. Tracheostomy may be required d. Surgery for cleft palate
e. Early intervention and multidisciplinary team approach f. Orthopedic care for skeletal anomalies
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CEREBRO-COSTO-MANDIBULAR SYNDROME 141
Fig. 1. An infant with cerebro-costo-mandibular syndrome (at birth and 12 weeks of age) showing severe micro/retrognathia and malfor- mations of the ribs with multiple gaps and segmentation defects.
