Article

Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.

Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Nature Genetics (Impact Factor: 29.65). 01/2011; 43(1):20-2. DOI: 10.1038/ng.724
Source: PubMed

ABSTRACT We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both alleles of POLR1C in three individuals with TCS. These findings identify two additional genes involved in TCS, confirm the genetic heterogeneity of TCS and support the hypothesis that TCS is a ribosomopathy.

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    ABSTRACT: Treacher Collins syndrome is an autosomal dominant disorder resulting in congenital craniofacial deformities. Scoliosis has not been previously reported as one of the extracranial manifestations of this syndromic condition. We present a 15-year-old British Caucasian girl with Treacher Collins syndrome who developed a severe double thoracic scoliosis measuring 102[degree sign] and 63[degree sign] respectively. The deformity was noted at age 14 years by the local general practitioner and gradually progressed until she was referred to our service and subsequently was scheduled for surgical correction. There were no congenital vertebral anomalies. As part of the condition, she had bilateral conductive hearing impairment. She also had reduced respiratory reserves and a restrictive lung disease. Both curves were rigid on supine maximum traction radiographs. She underwent a single-stage anterior and posterior spinal arthrodesis with pedicle hook/sublaminar wire/screw and rod instrumentation and autologous rib graft, supplemented by allograft bone and made a good postoperative recovery. Her scoliosis was corrected to 25[degree sign] and 24[degree sign] and a balanced spine in the coronal and sagittal planes was achieved. At latest follow-up beyond skeletal maturity (3 years post-surgery) she had an excellent cosmetic outcome with no loss of deformity correction, no detected pseudarthrosis and a normal level of activities. Scoliosis can occur in patients with Treacher Collins syndrome with the deformity demonstrating significant deterioration around the adolescent growth spurt. A high index of awareness will allow for an early diagnosis and scoliosis correction at a stage when this can be safer and performed through a single-stage posterior procedure. If the deformity is detected at a later age and stage of growth as occurred in our patient, more complex surgery is required and this increases the risk for major morbidity and potential mortality. Surgical treatment can correct the deformity, balance the spine and restore cosmesis, as well as prevent mechanical back pain and respiratory complications if the scoliosis progressed to cause severe thoracic distortion. A thorough preoperative assessment can diagnose associated comorbidities and reduce the risk for postoperative complications.

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