Biallelic pathogenic variants in the OTUD6B gene cause a multisystem disorder. A list of commonly reported features is included below. There has been a spectrum of phenotypic severity reported in previous patients.
Development and Cognition
• Global developmental delay and intellectual disability are present in all previously described patients. Intellectual disability is generally moderate to severe, with rare reports of mild intellectual disability.
• Many patients have a history of autism/autistic features
• Language impairment is common, with some patients achieving some language and others who are nonverbal
Neurologic and Musculoskeletal
• Seizures are present in the majority of patients, and seizures can be difficult to control in a subset of patients
• Some patients achieve ambulation, while others do not and/or use a wheelchair
• Ataxia, generally mild-moderate
• Hypotonia
• Skeletal manifestations can include scoliosis, short stature, distal limb anomalies and other mild skeletal anomalies
Gastrointestinal
• Failure to thrive and feeding difficulties, particularly in infancy
• Some patients require G-tube placement
• Chronic constipation
Physical Features
• Microcephaly
• Broad root and prominent nasal bridge
• Smooth, long philtrum
• Thin upper lip
• High arched palate
Other Features
• Intrauterine growth restriction and difficulties growing
• Cardiac defects have been reported in multiple patients, including atrial septal defect, ventricular septal defect, tetralogy of Fallot, pulmonic stenosis
• Dental anomalies can include small, widely spaced, crowded, or pointed teeth and bifid uvula
• Ophthalmologic manifestations can include myopia, strabismus, and astigmatism
• Renal anomalies
• Thyroid issues such as hypothyroidism (rarely)
• Abnormal immunoglobulins (rarely)
OTUD6B