BACKGROUND: Cutis laxa (CL) is a group of disorders characterized by loose, inelastic, and redundant skin. The different types of CL are distinguished by clinical features, inheritance, and molecular findings. The objective of this study was to characterize the pulmonary phenotype of the different types of CL based on age of onset (congenital, acquired/late-onset, or unknown) and mutational status. The first aim of this study was to collect clinical data to better define the pulmonary involvement in cutis laxa. The second aim was to determine if heterozygous carriers of recessive types of cutis laxa are susceptible to chronic lung disease. METHODS: Clinical questionnaires, medical histories, and pulmonary function tests (PFTs) were used to collect clinical data on patients with a confirmed or suspected diagnosis of CL and unaffected first-degree relatives with a known mutation (carriers). The clinical data was then compared between the groups categorized by age of onset and between those with known mutations (mutational status). RESULTS: The clinical questionnaires and medical histories of 83 CL patients with 8 acquired/late-onset, 52 congenital, and 23 of unknown etiology and 5 carriers were analyzed. In addition, mutations have been identified in 27 of the 83 patients in ELN, FBLN4, FBLN5, ATP6V0A2, or LTBP4, and the 5 carriers had mutations in either FBLN4 or LTBP4. The most common respiratory responses amongst the patients included pneumonia (24.1%), tachypnea (15.7%), and emphysema (12.0%). The only statistically significant finding was dyspnea in acquired/late-onset patients. Of those with a known mutation, 15 reported pulmonary involvement, with 10 of these individuals having at least one LTBP4 mutation. For the 13 PFTs collected, the 10 CL patients ranged from normal lung function to very severe obstruction, and 3 carriers were deemed to have normal function. An important new finding was the presence of pulmonary obstructive disease in those with ATP6V0A2 mutations. CONCLUSION: These results demonstrate a high prevalence and significant heterogeneity of pulmonary complications in CL. Further research is needed to determine any correlation between specific pulmonary findings and genotypes. PUBLIC HEALTH SIGNIFICANCE: Chronic lung disease is a common cause of morbidity in the general population. Uncovering the genetic basis of chronic lung disease in inherited syndromes has the potential to identify key molecular targets for improved diagnosis and treatment of common respiratory ailments.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04052011-233306 |
| Date | 29 June 2011 |
| Creators | Westman, Rachel E |
| Contributors | Robin Grubs, Juliann McConnell, Zsolt Urban, John Wilson |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04052011-233306/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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