Hatice Mutlu-Albayrak1, Nagehan Emiralioğlu2, Çağrı Damar3. 1. Department of Pediatric Genetics, Cengiz Gökcek Maternity and Children's Hospital, Gaziantep, Turkey. 2. Department of Pediatric Pulmonology, Hacettepe University Hospital, Ankara, Turkey. 3. Department of Pediatric Radiology, Gaziantep Medical Faculty Hospital, Gaziantep, Turkey.
Abstract
Background: Autosomal recessive cutis laxa type IC (ARCL1C) is characterized by cutis laxa accompanied by pulmonary, gastrointestinal, urinary, musculoskeletal involvement caused by biallelic mutations in latent transforming growth factor-beta binding protein 4 (LTBP4) gene. The overall prognosis is poor, and most patients die in infancy because of severe pulmonary emphysema (PE). Aim: We aimed to evaluate 3 ARCL1C patients, 2 of whom are still alive and in their childhood period, from 2 unrelated families with novel LTBP4 mutations, to demonstrate the clinical variability of pulmonary involvement. Materials and Methods: Three children who were molecularly confirmed by LTBP4 sequencing analysis were comprehensively reviewed in terms of pulmonary manifestations through chest examination, lung function tests (LFTs), chest X-ray, and thorax computed tomography. Results: Family 1 (c.3740A>G LTBP4 mutation): A 5-year-old male patient with pulmonary artery stenosis (PAS) presented with persistent cough and exhibited mild restriction on LFT. Family 2 (c.2T>G LTBP4 mutation): Radiographic examinations revealed PE in a 7-year-old female patient who was operated for diaphragmatic hernia. She had recurrent bronchiolitis and pulmonary infections. LFT revealed both obstructive and restrictive pattern. Her cousin also had respiratory distress with the onset of the newborn period and died due to bilateral pneumothorax in early infancy. Conclusion: The variable severity of pulmonary findings was shown in these patients. It should also be kept in mind that there could be intrafamilial variability of systemic manifestations. Although obstructive lung disease is expected to be seen in ARLC1C patients, restrictive LFT patterns may also be detected as a result of comorbidities such as diaphragmatic hernia and PAS.
Background: Autosomal recessive cutis laxa type IC (ARCL1C) is characterized by cutis laxa accompanied by pulmonary, gastrointestinal, urinary, musculoskeletal involvement caused by biallelic mutations in latent transforming growth factor-beta binding protein 4 (LTBP4) gene. The overall prognosis is poor, and most patients die in infancy because of severe pulmonary emphysema (PE). Aim: We aimed to evaluate 3 ARCL1C patients, 2 of whom are still alive and in their childhood period, from 2 unrelated families with novel LTBP4 mutations, to demonstrate the clinical variability of pulmonary involvement. Materials and Methods: Three children who were molecularly confirmed by LTBP4 sequencing analysis were comprehensively reviewed in terms of pulmonary manifestations through chest examination, lung function tests (LFTs), chest X-ray, and thorax computed tomography. Results: Family 1 (c.3740A>G LTBP4 mutation): A 5-year-old male patient with pulmonary artery stenosis (PAS) presented with persistent cough and exhibited mild restriction on LFT. Family 2 (c.2T>G LTBP4 mutation): Radiographic examinations revealed PE in a 7-year-old female patient who was operated for diaphragmatic hernia. She had recurrent bronchiolitis and pulmonary infections. LFT revealed both obstructive and restrictive pattern. Her cousin also had respiratory distress with the onset of the newborn period and died due to bilateral pneumothorax in early infancy. Conclusion: The variable severity of pulmonary findings was shown in these patients. It should also be kept in mind that there could be intrafamilial variability of systemic manifestations. Although obstructive lung disease is expected to be seen in ARLC1C patients, restrictive LFT patterns may also be detected as a result of comorbidities such as diaphragmatic hernia and PAS.
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