1.
To the Editor,
A 14‐year‐old adolescent girl presented with progressive exertional dyspnea for 3 years. She had undergone right inguinal hernioplasty at 6 years. Examination revealed cachexia, pallor, cyanosis, pandigital grade 3 clubbing, facial dysmorphism (receding hairline, periorbital fullness, loose sagging skin, and smooth philtrum), and hyper‐extensible joints with generalized loose sagging skin. She had hypoxemia (SpO2 75%), not responding to oxygenation, pectus carinatum, and decreased air entry in the left apical areas. Cardiovascular examination showed mediastinal shift to the right with features of pulmonary hypertension (PAH) (loud P2, parasternal heave, and pansystolic murmur on the tricuspid area). Baseline blood investigations were unremarkable. A chest X‐ray revealed hyperlucency in the left upper zone. CT thorax revealed left upper lobar overinflation and diaphragmatic hernia (Figure 1A,B). Echocardiogram showed a large ostium secondum‐atrial septal defect (ASD) of size 15 mm, and severe PAH (tricuspid regurgitation velocity = 3.8 m/s, pulmonary artery systolic pressure = 85 mmHg, dilated right atrium and ventricle). Cardiac catheterization established a bidirectional shunt at ASD, with absent response to oxygen supplementation/vasoreactivity testing, confirming Eisenmenger physiology. Barium swallow study and upper gastrointestinal endoscopy were suggestive of a paraesophageal hernia with multiple gastric diverticula. As there was persistent respiratory distress despite medications for PAH, left upper lobectomy was done, with the histopathology revealing marked alveolar overdistension and septal attenuation, consistent with emphysematous changes. An underlying connective tissue defect was suspected to be causative for the multi‐system involvement, and whole exome sequencing (WES) was ordered. WES suggested Urban‐Rifkin‐Davis syndrome (URDS) with a novel variant c.3512dup (p.Arg1172ProfsTer60) in exon 24 of the LTBP4 gene. Post‐lobectomy, her respiratory distress improved, with saturation improving to 85%, and she was discharged on low‐flow oxygen support. She is planned for hernia repair on follow‐up.
Figure 1.
(A) Axial section depicting left upper lobe hyperinflation (white arrow) with adjacent lung collapse (blue arrow). (B) Coronal image depicting the left posterolateral congenital diaphragmatic hernia with dilated esophagus (red arrow) and stomach (yellow arrow) in the thorax. [Color figure can be viewed at wileyonlinelibrary.com]
Cutis laxa is a rare multisystem connective tissue disorder, with an incidence of one in four million. Type 1C (also called URDS) is characterized by involvement of the skin, musculoskeletal, respiratory, cardiovascular, gastrointestinal, and genitourinary systems. The underlying pathogenesis is impaired elastogenesis and dysregulated TGF‐β signaling, resulting in structural fragility of parenchyma, diaphragm, and vasculature, and so forth [1]. Respiratory complications in URDS are often fatal during infancy, with a reported mean survival of 4 years [2, 3]. However, our child had a delayed presentation and survival into adolescence. Loss of function of LTBP4 impairs elastic fiber integrity, causing early onset emphysema, and the dysregulated TGF‐β signaling may further promote abnormal lung development and vascular remodeling, contributing to pulmonary hypertension [1]. Childhood emphysematous lung diseases have only limited causes, including congenital lobar emphysema, alpha‐1 antitrypsin deficiency, and congenital syndromes (Marfan, Ehlers‐Danlos, Cutis Laxa) [4]. The most prevalent cardiovascular association is pulmonary artery stenosis, followed by ASDs, as in our case [3]. The Eisenmenger syndrome, in our case, could be due to a combination of underlying long‐standing ASD and chronic parenchymal lung disease. The variant is a novel “likely pathogenic variant” (as per ACMG criteria), which has not been reported [5]. Comprehensive evaluation is required in URDS, including echocardiography (cardiac defects and pulmonary hypertension), and also for gastrointestinal and diaphragmatic anomalies.
To conclude, a high index of suspicion for URDS should be kept in a child with lobar overinflation, characteristic facial dysmorphic features, loose skin, and other syndromic associations.
Author Contributions
Kkomal C. Suvarna: writing – original draft. Kalyana Prabhakaran: visualization, validation. Sathya Srivatsav: visualization, validation. Taruna Yadav: data curation, software, visualization. Prawin Kumar: project administration, supervision. Jagdish Prasad Goyal: supervision, writing – review and editing.
Funding
The authors have nothing to report.
Ethics Statement
As per the AIIMS Jodhpur policy, ethical approval is not required for case reports/images.
Consent
Informed consent was obtained from the parents, and they permitted us to publish clinical images.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
The authors have nothing to report.
Data Availability Statement
The authors have nothing to report.
References
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Associated Data
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Data Availability Statement
The authors have nothing to report.