Pulmonary Manifestations of Genetic Conditions & Congenital Lung Malformations

Multiple genetic conditions and congenital malformations lead to functional and structural disorders of the pediatric lung and negatively affect respiratory mechanics. This section provides a broad overview of other important pulmonary diseases (primary ciliary dyskinesia, neuromuscular disease, congenital pulmonary malformations). ChILd and CF are discussed in detail elsewhere in this guide.

Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder of ciliary structure and function associated with several mutations of genes encoding ciliary proteins. PCD affects as many as 1 in 60,000 live births in the United States. Due to impaired or absent mucociliary airway clearance, patients with PCD may develop recurrent sinopulmonary infections leading to bronchiectasis, pulmonary fibrosis, and obstructive lung disease. Many patients present in infancy with respiratory distress or recurrent pneumonia. In addition to the pulmonary manifestations of PCD, some patients have other issues associated with ciliary dysfunction, including recurrent ear infections, situs inversus, and infertility. Consensus guidelines published in 2016 by the PCD Foundation recommend using a combination of genetic testing, electron microscopy, and nasal nitric oxide for the diagnosis of PCD. Management of PCD-associated lung disease consists of airway clearance therapies and antibiotics.

Created by Kevin Gipson

Neuromuscular Diseases

Neuromuscular disorders, such as Duchenne muscular dystrophy and spinal muscular atrophy, affect the muscles of the respiratory “pump.” Children affected by these disorders may experience severe and progressive diminution of diaphragmatic muscle tone and are at risk of developing ventilatory insufficiency and carbon dioxide retention. This progression may require noninvasive positive-pressure ventilation or even tracheostomy for long-term mechanical ventilation.

Normal cough and airway clearance are negatively impacted in neuromuscular disease. Therefore, mechanical airway-clearance devices are commonly used. Pulmonary-function testing generally demonstrates a restrictive pattern as neuromuscular disease progresses and should be performed every 6 months. Polysomnography may identify patients at risk for hypoventilation and other sleep disturbances.

(Reprinted from The Lancet, Respiratory assessment (in the clinic) of patients with Duchenne muscular dystrophy. From: Bushby K, et al. Diagnosis and Management of Duchenne Muscular Dystrophy, Part 2: Implementation of Multidisciplinary Care. The Lancet Neurology 2010, with permission from Elsevier.)

Currently, the goals of pulmonary management are optimizing airway clearance and minimizing infections with the aim of maintaining lung function and minimizing decline. Several promising genetic therapies are now being deployed in clinical trials and may markedly alter the presentation and progression of disease.

Congenital Pulmonary Malformations

Congenital malformations of the lung are relatively rare but can have significant clinical manifestations. This group of lesions consists of congenital pulmonary airway malformations (CPAM), congenital lobar emphysema, bronchogenic cysts, and bronchopulmonary sequestrations. Such lesions can act as space-occupying masses and as niduses for infection, leading to impaired respiratory mechanics and recurrent pneumonia.

(Source: Congenital Pulmonary Malformation in Children. Scientifica 2012. Copyright © 2012 Montasser Nadeem et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

With the advent of advanced prenatal ultrasonography, congenital pulmonary airway malformations (CPAM) and pulmonary sequestrations can be diagnosed in utero. A proportion of cases are diagnosed postnatally by chest radiograph or chest CT scan in infants in neonatal respiratory distress or in later childhood after repeated pulmonary infections or refractory wheeze.