Pregnancy, birth and infancy are usually unremarkable, although early hypotonia is sometimes a feature. No major congenital abnormalities or medical problems have been observed.
Delayed motor, speech, cognitive and social milestones are usually the first cause for concern. Children with ZDHHC9 variants tend to have marked problems with motor co-ordination and sustained attention. A discriminating feature from other causes of neurodevelopmental delay is persistent speech problems including quiet voice, poor articulation, slow and inaccurate sequencing of speech sounds. These lead to marked problems with expressive communication, beyond expectation for receptive comprehensive and nonverbal cognition. Literacy skills are also very delayed. In some cases, expressive language problems have been misdiagnosed as severe intellectual disability or autism (which is not a common feature of ZDHHC9).
A high proportion of individuals with ZDHHC9 variants have childhood-onset epilepsy. Most frequently, they develop Rolandic seizures (night-time oromotor and upper limb seizures, sometimes with secondary generalization). Sleep disturbance can also be a feature, in which case possible epilepsy should be considered. Other seizure types that have been reported include infrequent generalized tonic-clonic seizures, adult-onset Rolandic seizures, and in one case more severe generalized epilepsy with status epilepticus and later severe intellectual disability.
Minor dysmorphic facial features (pinched nose, round cheeks) are sometimes observed in individuals with ZDHHC9, but these are not highly consistent. Physical features similar to Marfan Syndrome (pes planus, pectus carinatum, arachnodactyly) were described in some of the early reported cases. However, these physical features are not consistent across individuals with this diagnosis and their absence does not rule it out. Medical manifestations of Marfan Syndrome have not affected any individuals with ZDHHC9 variants. Strabismus and hypermetropia do seem to be common features.