Au-Kline Syndrome

CLINICAL CHARACTERISTICS

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. Congenital heart disease, hydronephrosis, palate abnormalities, and oligodontia are reported in the majority of affected individuals. Variable autonomic dysfunction (gastrointestinal dysmotility, high pain threshold, heat intolerance, recurrent fevers, abnormal sweating) is found in more than one third of affected individuals. Additional complications can include craniosynostosis, feeding difficulty, vision issues, hearing loss, osteopenia, and other skeletal anomalies. Epilepsy and brain malformations are rare.

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

MANAGEMENT

Physical therapy may be helpful for hypotonia. Feeding therapy for poor weight gain; gastrostomy tube placement may be required for persistent feeding issues. Referral to neurologist with experience in management of autonomic dysfunction. Bisphosphonate treatment could be considered for those with osteopenia who experience recurrent fractures. Standard treatment for developmental delay / intellectual disability, behavior concerns, epilepsy, craniosynostosis, palatal anomalies, congenital heart defects / aortic dilatation / cardiomyopathy, hydronephrosis, cryptorchidism, bowel dysfunction, skeletal anomalies, refractive errors, keratopathy, hearing loss, malocclusion / open bite, oligodontia, hypothyroidism, hypoventilation, and obstructive sleep apnea. Anesthesia consultation is suggested prior to any sedation for surgery given potential airway issues from malocclusion and macroglossia. There is also potential risk that prolonged intubation and ventilation will be required, as occurred in one individual after surgery. At each visit, measure growth parameters and evaluate nutritional status; monitor developmental progress and educational needs; assess for neurobehavioral/psychiatric manifestations; monitor those with seizures; assess for signs and symptoms of sleep apnea. At all health visits in the first few months of life, screen for craniosynostosis. At all health visits and at least annually, assess for new manifestations, such as seizures or dysautonomia; clinical examination for scoliosis. At least every 6 months, dental and/or orthodontic evaluation. Annually, TSH and free T. Annually or as clinically indicated, audiology evaluation. The frequency of echocardiogram and assessment for cardiomyopathy should be determined by a cardiologist. The frequency of ophthalmology evaluations should be determined by an ophthalmologist. Consideration of bone densitometry is based on the severity of osteopenia and history of fractures.

GENETIC COUNSELING

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 pathogenic variant. Each child of an individual with Au-Kline syndrome has a 50% chance of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk is possible if the pathogenic variant in the family is known.