USP7-Related Disorder. Hao-Fountain syndrome.
Incidence
The syndrome is inherited in an autosomal dominant pattern. However most cases recorded so far have been the result of de novo or new mutations in the gene. Mutations in USP7 are either gene deletions, meaning the entire gene is missing, or point mutations, meaning just one letter in the DNA code is changed. As of March 2021, there are 82 known Hao-Fountain patients worldwide. The disease\'s incidence and prevalence remain unknown. Patients with this disorder often go undiagnosed or misdiagnosed. It was officially named Hao-Fountain Syndrome in 2020. It has also been called HAFOUS and Chromosome 16p13.2 Deletion Syndrome.
Clinical Characteristics
This gene mutation disorder is a neurodevelopmental condition. Symptoms can vary according to the individual affected, not all symptoms present in all individuals, and symptoms may vary according to their severity. The syndrome presents with both physical and behavioral features. Changes in the USP7 gene are responsible for the syndrome. This gene is a protein-coding gene that is responsible for tumor suppression, and the body’s immune response amongst other roles. The changes to the gene are usually point mutations or gene deletions. Developmental delay is common, particularly speech delay. Some individuals affected by the syndrome never learn to speak. Intellectual disability and developmental delay are also main symptoms. Many individuals also have behavioral issues, ranging from aggressive behavior to impulsivity and compulsivity). Others are also found to be on the autism spectrum, and to have ADHD. Unique physical features of the syndrome include dysmorphic facial features, a short stature and issues with the eyes (esotropia, myopia, strabismus, nystagmus). Small hands and feet are also characteristic of the syndrome. Other symptoms may include seizures, low muscle tone both in infancy and into adulthood, sleep apnea and troubles sleeping, scoliosis and contractures (bent joints). It has many of the features of Prader-Willi syndrome. Approximately half of the known patient population suffers from epilepsy. Other symptoms include developmental delay/intellectual disability, autism spectrum disorder, abnormal brain MRIs, speech impairment, hypotonia, gastrointestinal issues, and eye anomalies.
Precipitants
None
Provocation Tests
None.
Diagnostic Procedures
USP7 mutations are diagnosed through either whole exome sequencing, USP7 sequencing, or chromosome microarray analysis. Chromosome microarray testing can detect if the entire USP7 gene or pieces of the gene are missing (deleted), but misspellings within the USP7 gene will not be detected. Whole exome sequencing can identify a diagnosis of a USP7-related disorder by detecting even very small DNA mutations of a single letter (point mutations) in the USP7 gene.