So far, only 5 cases (age 10 months to 20 years) have been reported in literature.
The major clinical features are:
Global developmental delay apparent from infancy
The IQ levels vary from mild to moderate intellectual disability.
Behavioral and sleeping problems
ADHD, autistic features, anxiety and temper tantrums have been observed. In three individuals a sleep apnoea was present.
Dysmorphisms
A recognisable facial gestalt including a (relative) macrocephaly, a high and broad forehead and hypertelorism.
Macrocephaly and growth disturbance
Leading to a head circumference of + 2,5 SD to +4 SD in childhood.
Two patients had a failure to thrive and short stature.
Cardiovascular abnormalities
Various congenital heart defects may be present, such as ASD, VSD, PS, PDA, or bicuspid aortic valve.
Endocrine abnormalities
Hypothyroidism has been reported in two patients and another patient required testosterone treatment.
Epilepsy
Two patients had epilepsy.
Other
Cleft lip/palate (1x), multicystic kidney dysplasia (1x), visus abnormalities (4x).
Penetrance
Penetrance is 100%. So far, all individuals with a de novo pathogenic variant in SPOP that result in a dominant-negative effect manifest intellectual disability and additional variable clinical features.
SPOP LoF