Targeted syndrome/gene under study:

OMIM # 617762


We have identified previously unreported 35 affected individuals from 32 unrelated families with biallelic variants in ACER3. The manifesting symptoms frequently included global developmental delay, motor regression, lower limb spasticity with gait impairment, frequent falls and loss of ambulation, dysarthria, and dysphagia. Among the frequent neurological findings were GDD/Intellectual disability, axial hypotonia, appendicular spasticity in, muscle weakness, feeding difficulties, and limb dystonia. Brain MRI available from 15 cases showed leukodystrophy. The levels of the major glycerophospholipids, neutral lipids, and sphingolipids from control and ACER3 fibroblasts were determined by lipidomics. This study is aimed at delineating the phenotypic spectrum of recently described and poorly characterized gene-disease association. We are interested in families with biallelic ultra-rare variants in ACER3. We would like to receive detailed clinical data, brain MRI images, video of the patients for a deeper phenotyping, genetic data with segregation analysis, and skin biopsies for functional studies.

Coordinating clinicians

Dr. Reza Maroofian –

Dr. Rauan Kaiyrzhanov – 


Institute of Neurology, University College London, London, UK 

Specific requirements beyond clinical data and genotype data sharing:

1- Re-analysis of DNA samples: No

2- Resampling of patients: No

3- Linked to a translational/basic research project: No