The first signs of PREPLdeficiency typically occur in the neonatal period, when severe hypotonia and feeding problems quickly become evident. Some infants have needed short-term respiratory support. Eyelid ptosis is nearly always present. The feeding problems often necessitate tube feeding, which can typically be stopped during infancy.
The hypotonia improves gradually, and children learn to walk around 18 months of age. Residual motor weakness is observed to a variable degree in the cranial region resulting in a nasal dysarthria and myopathic facial characteristics. Eyelid ptosis also persists, as well as variable mild muscle weakness in proximal muscles.
At childhood age, appetite for food and food intake often increase, resulting in overweight unless dietary intervention is started. Around this age, patients often develop growth hormone deficiency with slowing of growth, but the age of onset varies considerably.
Learning problems frequently occur and educational support or special education can be necessary. Mean IQ is around 70, but children with PREPLdeficiency can have normal IQ.
Other characteristics are a dry mouth and hypergonadotropic hypogonadism.
Mild dysmorphic features occur, including an arched palate and a narrow bitemporal diameter. In combination with the eyelid ptosis and the myopathic facial features that are frequently present, these features can help to consider the diagnosis.
In a few case reports, variable cardiac abnormalities have been reported, but a firm link with PREPLdeficiency has not been established yet.
PREPL