Growth parameters
Most individuals with a mutation in FBXO11 had a normal stature, but short and tall stature has been described with short stature seeming to be more prevalent. In a subset of individuals obesity has been observed.
Most individuals had normal head circumference, but both microcephaly and macrocephaly have been described.
Feeding difficulties are described in a subset of individuals.
Neurological features
All individuals had mild to severe developmental delay characterized by delayed motor- and speech development to severe ID.
Brain abnormalities have been seen in less than half of the individuals of which ventriculomegaly was the most common brain abnormality whilst white matter abnormalities have also been reported. Other types of brain abnormalities can be present but are relatively rare in the cohorts described by Gregor et. al. and Jansen et. al.
More than half of the affected individuals presented with muscular hypotonia.
Part of the individuals presented with seizures. Several types of seizures have been observed per individual including generalized tonic-clonic seizures, atonic seizures, myoclonic seizures, absence seizures, focal seizures and nocturnal seizures.
Neuropsychological features
A large portion of individuals exhibited behavioural problems, these encompassed autism spectrum disorder (ASD), ADHD, aggression, anxiety, difficulties with social interaction and repetitive hand movements. Furthermore, sleeping difficulties were prevalent.
Facial dysmorphisms
The most frequently observed facial features were a thin upper lip with a broad prominent space between the paramedian peaks of the upper lip, a high broad forehead and long or downslanting palpebral fissures with laterally everted lids and long eyelashes. Although some individuals did show resemblance in facial characteristics, no distinct facial gestalt could be established based on the currently described individuals.
Musculoskeletal abnormalities
Skeletal abnormalities reported were often minor and involved the hand or feet, such as brachydactyly, clinodactyly, tapering fingers, fetal fingertip pads and abnormal of the hands and/or feet. Also, hyperlaxity of the joints and scoliosis have been reported.
Gastro-intestinal problems
Gastro-intestinal problems, including feeding difficulties, vomiting, gastroesophageal reflux and constipation were seen.
Immunology
Recurrent otitis media and respiratory infections have been reported.
Vision problems
Vision problems occurred in approximately half of the individuals described, these mainly included strabismus while hypermetropia has also been reported. Other types of vision problems were rare.
Congenital heart malformations
Congenital heart malformations were very rare. Two individuals had an atrial septal defect. Additionally, one individual was reported to suffer from cardiomyopathy.
Renal and urogenital anomalies
Renal and urogenital malformations were incidentally described, including cryptorchidism, coronal hypospadias and hydronephrosis.
Additional features
Abnormal hair growth patterns and abnormal skin pigmentation were present in a small subset of individuals.
FBXO11