GeneReviews®

Au-Kline syndrome is characterized by developmental delay and hypotonia with moderate-to-severe intellectual disability, and typical facial features that include long palpebral fissures, ptosis, shallow orbits, large and deeply grooved tongue, broad nose with a wide nasal bridge, and downturned mouth. There is frequently variable autonomic dysfunction (gastrointestinal dysmotility, high pain threshold, heat intolerance, recurrent fevers, abnormal sweating). Congenital heart disease, hydronephrosis, palate abnormalities, and oligodontia are also reported in the majority of affected individuals. Additional complications can include craniosynostosis, feeding difficulty, vision issues, osteopenia, and other skeletal anomalies.

The diagnosis of Au-Kline syndrome is established in a proband by identification of a heterozygous pathogenic variant in HNRNPK on molecular genetic testing.

Treatment of manifestations: Physiotherapy support may be helpful for hypotonia; dysautonomia management per neurologist; standard treatment for congenital heart defects; cleft palate treatment per craniofacial specialists; early intervention, individualized education, and therapies for developmental delay; psychiatry referral for those with behavior issues; nasogastric or gastric-tube feeding as needed for significant feeding issues; treatment of hearing loss with hearing aids if necessary; standard treatment for refractive errors and keratopathy; standard dental and/or orthodontic care as needed; orthopedics referral for scoliosis as needed for bracing or surgical intervention; standard management for hypothyroidism; bisphosphonate treatment could be considered for recurrent fractures. Prevention of secondary complications: Anesthesia consultation is suggested prior to any sedation for surgery given potential airway issues from malocclusion and macroglossia and risk for prolonged intubation and ventilation. Surveillance: Screen for craniosynostosis in infants at each health visit during the first few months of life; at all health visits and at least annually review developmental milestones and screen for seizure history, symptoms of dysautonomia, behavior concerns, and scoliosis; annual audiologic evaluation; echocardiography to monitor for aortic dilatation with frequency as per cardiologist; ophthalmologic evaluation with frequency as per ophthalmologist; periodic TSH and bone densitometry as needed.

Au-Kline syndrome is inherited in an autosomal dominant manner. All probands reported to date with Au-Kline syndrome have the disorder as a result of a de novoHNRNPK pathogenic variant. Each child of an individual with Au-Kline syndrome has a 50% chance of inheriting the HNRNPK pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the HNRNPK pathogenic variant in the family is known.