Cerebro–costo–mandibular syndrome: Clinical, radiological, and genetic findings

Abstract

Cerebro-Costo-Mandibular syndrome (CCMS) is a rare autosomal dominant condition comprising branchial archderivative malformations with striking rib-gaps. Affected patients often have respiratory difficulties, associated with upper airway obstruction, reduced thoracic capacity, and scoliosis. We describe a series of 12 sporadic and 4 familial patients including 13 infants/children and 3 adults. Severe micrognathia and reduced numbers of ribs with gaps are consistent findings. Cleft palate, feeding difficulties, respiratory distress, tracheostomy requirement, and scoliosis are common. Additional malformations such as horseshoe kidney, hypospadias, and septal heart defect may occur. Microcephaly and significant developmental delay are present in a small minority of patients. Key radiological findings are of a narrow thorax, multiple posterior rib gaps and abnormal costo-transverse articulation. A novel finding in 2 patients is bilateral accessory ossicles arising from the hyoid bone. Recently, specific mutations in SNRPB, which encodes components of the major spliceosome, have been found to cause CCMS. These mutations cluster in an alternatively spliced regulatory exon and result in altered SNRPB expression. DNA was available from 14 patients and SNRPB mutations were identified in 12 (4 previously reported). Eleven had recurrent mutations previously described in patients with CCMS and one had a novel mutation in the alternative exon. These results

Further Observations in Cerebro-Costo-Mandibular Syndrome: Exploration with CT Imaging

“…6 Extent of rib changes is variable from single focal posterior defect to extensive changes involving most of the ribs, leading to flail chest. 3,7 Forth to tenth ribs are usually involved. 1 These defects often result in a bell-shaped thorax and may lead to underlying lung hypoplasia, compounding upper-airway obstruction.…”

“…Abnormal costotransverse artic-ulations were shown on CT in a patient with extensive rib involvement. 3 Postnatal growth retardation and microcephaly are common findings. 3,8 Central nervous system changes of hypoxic ischemic nature can occur due to prolonged respiratory insufficiency.…”

“…3 Postnatal growth retardation and microcephaly are common findings. 3,8 Central nervous system changes of hypoxic ischemic nature can occur due to prolonged respiratory insufficiency. Other less common reported findings include hearing loss, tracheal, hyoid cartilage ossification abnormalities, 3 choanal atresia, elbow and clavicular hypoplasia, scoliosis, pterygium colli, renal and central nervous system developmental disorders such as spina bifida.…”

“…Defects in the SNRPB gene on the chromoso-me20p13 are responsible for these developmental anomalies (OMIM: 117650). 1,3 Differential diagnoses of the condition include trisomy 13 and 18 and Pierre Robin sequence. Most of the orofacial anomalies and airway changes appear to represent Pierre Robin sequence and lead to respiratory difficulty and early mortality.…”

Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations

“…Heterozygous deletion of FOXC1 in 6p25.3 (cases 28 and 32) can lead to Axenfeld-Rieger syndrome (6p25 deletion syndrome); ocular hypertelorism and at midface are prevalent in affected postnatal cases [22]. [24,25]. However, to date, there is no evidence supporting their pathogenicity in haploinsu ciency.…”