Clinical Guidance
The cardinal features of Tatton-Brown-Rahman syndrome (TBRS) are overgrowth and mild-to-severe intellectual disability. Other common features include joint hypermobility, obesity/ increased weight, hypotonia, behavioral/psychiatric problems, kyphoscoliosis, and seizures. To date, more than 90 individuals with a pathogenic variant in DNMT3A have been reported [, , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports and the authors' personal communications with the families. Table 2. Select Features of Tatton-Brown-Rahman Syndrome
Feature | % of Persons w/Feature | Comment |
|---|
Intellectual disability | 100% | Most often in mild-to-moderate range |
Overgrowth1 | 80% | Tall stature (height ≥2 SD above mean) in ~70% |
Macrocephaly (head circumference ≥2 SD above mean) in ~50% Joint hypermobility | ~75% | — |
Overweight2 | ~65% | — |
Hypotonia | ~55% | — |
Behavioral/psychiatric issues | ~50% | Most commonly autism spectrum disorder |
Kyphoscoliosis | ~30% | — |
Seizures | ~20% | — |
Cryptorchidism | ~20% of males | — |
Cardiovascular disease | ~10% | Most commonly congenital heart disease, although aortic root dilatation also observed |
Ventriculomegaly | 10% | — |
Chiari malformation | 10% | — |
Malignant tumors | ~5% | Most commonly acute myeloid leukemia3 SD = standard deviation(s) 1. Defined as length/height and/or head circumference ≥2 SD above the mean for age and sex 2. Defined as weight ≥2 SD above the mean for age and sex 3. Growth. Overgrowth is present in more than 80% of affected individuals. |
Source: GeneReviews — "Tatton-Brown-Rahman Syndrome"
