The major clinical findings observed in individuals with a heterozygous pathogenic variant in the DEAF1 gene are:
Intellectual disability (ID)
All patients have developmental delay/intellectual disability reported as moderate to severe. Developmental problems affect especially speech development, although motor delay is also present. Regression was observed in some individuals.
Additional neurological disorders
An abnormal walking pattern was found in the majority of reported patients, including ataxia. Sleeping problems were also frequently reported. Hypotonia, seizures and high pain threshold were observed in approximately half of the patients. Brain MRI may be abnormal.
Behavioral and psychiatric problems
Severe behavioral problems are observed, namely mood swings, an autism-like behavior (e.g. poor eye contact), aggressive behavior (e.g. self-injurious behavior), compulsive behavior and hyperactive behavior. Patients may also have a friendly behavior with a happy disposition.
Dysmorphisms
Mild facial dysmorphisms common to the majority of patients include thin and/or fair hair, straight eyebrows, full nasal tip, cupid’s bow in the upper lip, full lower lip and prominent chin. Common dysmorphisms in the extremities are fetal finger pads, syndactyly 2-3 of toes and pes planus.
Additional features
Other reported clinical manifestations are recurrent infections, genital anomalies, gastrointestinal problems as gastroesophageal reflux and constipation, mild low frequency hearing loss and hyperlaxity.
A comprehensive and up-to-date spectrum of clinical characteristics observed in patients with DEAF1-related syndrome is available in Charts and Graphs.
Penetrance
Penetrance is 100%. So far, all individuals with a heterozygous pathogenic variant in DEAF1 manifest intellectual disability.
Variable expressivity
Nevertheless, the severity of these clinical features and the occurrence of additional clinical features is variable among individuals with a heterozygous DEAF1 pathogenic variant. Thus, it is difficult to predict the degree of intellectual disability and which additional clinical manifestations a patient with a pathogenic variant in the DEAF1 gene will develop solely based on his/her genotype.
Differential Diagnosis
Angelman syndrome, Smith-Magenis syndrome and MECP2-related syndrome have been primarily considered in the differential diagnosis of patients with a heterozygous pathogenic variant in the DEAF1 gene.