Au-Kline syndrome

Au-Kline syndrome is a multi-system developmental condition characterized by a range of clinical features including global developmental delay, distinctive craniofacial features, and abnormalities affecting the kidneys and musculoskeletal system. The condition is associated with pathogenic variants in the HNRNPK gene. It primarily presents during infancy with features such as feeding difficulties and developmental challenges that prompt clinical evaluation. This condition is very rare, affecting fewer than 1 in 1,000,000 people.

Individuals with Au-Kline syndrome typically present with consistent features such as global developmental delay, thickened nuchal skin fold, cryptorchidism, feeding difficulties, vertebral segmentation defect, and a sacral dimple. As the condition evolves, some may also experience chronic kidney disease, gastroesophageal reflux, sagittal craniosynostosis, hip dysplasia, absent speech, and hypotonia, together with several craniofacial and skeletal differences including downslanted palpebral fissures, retrognathia, and a wide nasal ridge. Cognitive challenges and other neurodevelopmental issues are common, though not all individuals experience all features and severity varies considerably.

Au-Kline syndrome is caused by pathogenic variants in the HNRNPK gene, which plays an important role in RNA processing and regulation of gene expression. Disruption of this gene can lead to abnormalities in protein production and impact multiple organ systems. The condition is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene is sufficient to cause the disorder. Genetic counseling is recommended for affected families as the variant may be passed on to offspring, and the specific clinical presentation can vary even among family members.

Currently, management of Au-Kline syndrome focuses on supportive care and addressing individual symptoms through a multidisciplinary approach. Treatment is tailored to the specific needs of each individual and may include therapies to support feeding, developmental progress, and musculoskeletal or renal concerns. Regular surveillance is an essential part of long-term care, helping to detect potential complications at an early stage. Patients and families are encouraged to discuss personalized treatment options with their healthcare team, and genetic counseling is recommended as part of comprehensive care.

Outcomes in Au-Kline syndrome vary depending on the severity of symptoms, age at diagnosis, and access to specialized care. The condition may follow a variable course, with some individuals experiencing periods of stabilization after initial challenges. With current standards of care, many individuals can achieve improvements in quality of life despite ongoing developmental and medical challenges. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists familiar with this condition.