diaphragmatic hernia 4, with cardiovascular defects

Diaphragmatic hernia 4, with cardiovascular defects, is an inherited condition that primarily affects the development of the diaphragm and the cardiovascular system. It is associated with a range of structural and developmental abnormalities that can impact the lungs, heart, and other organ systems. Pathogenic variants in the ALDH1A2 gene are implicated in this disorder. Although exact prevalence data are not available, the condition is recognized as one with multisystem involvement and variable severity.

The clinical presentation of this condition is multisystem in nature. A hallmark feature is pulmonary hypoplasia, which is always present, and many affected individuals also experience signs of lung underdevelopment such as pulmonary arterial hypertension and pulmonary artery hypoplasia. Cardiovascular anomalies are common, with features such as a ventricular septal defect, aortic root aneurysm, and aortopulmonary collateral arteries occurring in a significant subset of patients. Additionally, musculoskeletal and facial characteristics including a bulbous nose, short chin, clinodactyly of the 5th finger, webbed neck, and finger as well as 2-3 toe syndactyly have been reported, while other features such as hepatomegaly, recurrent infections, optic nerve hypoplasia, and diaphragmatic eventration appear variably. Not all individuals experience all of these features, and severity varies considerably.

This condition is caused by alterations in the ALDH1A2 gene, which plays a critical role in the synthesis of retinoic acid, a molecule important for proper diaphragm and cardiovascular development. It is inherited in an autosomal recessive pattern, meaning that affected individuals have inherited two altered copies of the gene, one from each parent. Consequently, when both parents are carriers, there is a one in four chance with each pregnancy for the condition to occur. Genetic counseling is recommended for families to understand the risks and options for future family planning.

Currently, management focuses on supportive care and symptom management tailored to the individual’s clinical presentation. Treatment typically involves a multidisciplinary team to address the respiratory, cardiovascular, and musculoskeletal challenges that may arise. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. In addition, genetic counseling is advised to help families understand the condition and to discuss available care options with specialists.

Outcomes for individuals with diaphragmatic hernia 4, with cardiovascular defects, vary widely and depend on the severity of the features as well as access to specialized care. With current standards of care and ongoing advances in supportive treatments, many individuals benefit from a multidisciplinary approach that improves quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and relevant specialists, as well as support groups, to obtain personalized guidance and stay informed about evolving care strategies.