Clinical Guidance
USP7-related Hao-Fountain syndrome is characterized by developmental delay/ intellectual disability (mild to severe), hypotonia, and infantile feeding difficulties. Brain MRI anomalies, primarily affecting the white matter, are present in a majority of individuals. Contractures and genitourinary anomalies are present in a subset of affected individuals. However, none of these features are specific to USP7-related Hao-Fountain syndrome, and affected individuals exhibit broad variability. To date, more than 250 individuals have been identified with a pathogenic variant in USP7 [, , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Select Features of USP7-Related Hao-Fountain Syndrome
Feature | % of Persons w/Feature | Comment |
|---|
Developmental delay | 100% | — |
Intellectual disability | 50% | Most of those w/full-scale IQ 85 show specific learning disabilities. |
Muscular hypotonia | 73%-79% | This may transition to high muscle tone in later life. |
Autism spectrum disorder | 72% | — |
Brain MRI anomalies | 68%-73% | White matter paucity, hypoplastic corpus callosum |
Abnormal/unsteady gait | 66% | — |
Feeding difficulties | 55% | — |
Dental issues | 55% | — |
Impaired bone mineralization | 54% | May lead to fractures |
Eye anomalies | 53%-65% | Strabismus, refractive errors, nystagmus |
Sleep disturbance | 47% | Sleep apnea is present in almost 1/3 of affected persons. |
Epilepsy | 40% | — |
Hyperphagia | 39% | Mild to moderate |
Macrocephaly | 35% | — |
GERD | 37%-50% | — |
Hypogonadism | 25%-44% (males) | Incl micropenis /or undescended testes in males |
Contractures | 24% | — |
Hearing loss | 15% | GERD = gastroesophageal reflux disease; IQ = intellectual quotient Developmental delay and intellectual disability are common among affected individuals. |
Source: GeneReviews — "USP7-Related Hao-Fountain Syndrome"
