What are the symptoms of DHDDS?


Symptoms of DHDDS

As the DHDDS mutation was only confirmed to be a pathogenic gene with neurodevelopmental and sometimes neurodegenerative consequences in 2021 there is still a lot to learn about its symptoms and longer-term manifestation. Currently we only know of just over 70 cases of DHDDS mutations with neurodevelopmental manifestations worldwide, but that number is growing all the time.
It appears to be a spectrum disorder with symptoms ranging from mild to severe. Scientists do not yet understand why this is. The largest study of the DHDDS gene mutation to date with a cohort of 25 patients was done by Serena Galosi and team at Sapienza University and they published the following symptom profile.

From current clinical studies most patients (over 85%) suffer with the following to varying degrees:
- Learning difficulties ranging from mild to severe
- Tremor/myoclonus
- Seizure (ranging from absence, tonic-clonic, myoclonic, atonic, myoclonic-atonic, tonic to focal)
Over 70% suffer with ataxia
Other less common symptoms reported (less than 30%) include parkinsonism, dystonia, dysarthria, autistic traits, hyperactivity/ inattention, anxiety disorders, pyramidal signs, chorea, behaviour disorders, psychosis, stereotypies, OCD.

Not all patients will have all symptoms. Many patients have been reported as being stable for decades, but others can also experience a slow and variable neurological decline or more rapid neurological regression.
Mutations in the NUS1 gene which shares the role of dolichol synthesis with DHDDS seems to overlap in particular with DHDDS in terms of the clinical spectrum of presentation due to the converging pathway that they share.


Figure 1. Phenotypic spectrum associated with de novo DHDDS variants. (A) Prevalence of signs and symptoms in patients with de novo DHDDS variants (n = 25)

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