Pathogenic variants in the FBXW7 gene cause a neurodevelopmental disorder with considerable phenotypic heterogeneity.
Most individuals with the mutation FBXW7 gene have these features:
● Global developmental delay and intellectual disability
○ Ranging from borderline to severe
● Neurological issues
○ Hypotonia
○ Seizures
○ Macrocephaly
● Gastrointestinal issues
○ Feeding difficulties
○ Constipation
● Variable brain structural abnormalities (on CT and MRI)
○ Absent, hypoplastic or dysplastic corpus callosum
○ Abnormal cerebellum
○ Delayed myelination
○ Thick brainstem
○ Polymicrogyria
○ Scattered small subcortical calcifations
Uncommon features in individuals:
● Ophthalmological features such as strabismus and abnormality of refraction
● Ataxia
● Microcephaly, although more commonly macrocephaly
● Abnormal palatal, uvular or laryngeal morphology
● Cardiac anomalies
● Cryptorchidism
● Neutropenia
There are no recognisable facial features, however some individuals had features of:
● Deeply set eyes with upper eyelid fullness
● Cleft or high palate
● Midface retrusion with class III malocclusion
● Tall or broad forehead
● Cutaneous Blaschkoid dyspigmentation