Professionals

Clinical features
Patients with a confirmed HACE1mutation present with Spastic Paraplegia and Psychomotor Retardation with or without Seizures (SPPRS). They display lower limp spasticity and dystonia and are often non-ambulatory, as well as presenting with acquired microcephaly and intellectual disabilities ranging from moderate to severe. Epilepsy, skeletal deformities including kyphosis, lordosis, and short stature, obesity, minor facial deformities, speech delay, ocular abnormalities, and hearing loss have also been reported.

Prevalence
HACE1mutations and SPPRS are considered very rare genetic disorders, with case numbers too low to estimate a global frequency. The disorder was initially identified in a UK-based study of 4125 families (4295 patients) with severe developmental disorders, where HACE1mutations were found in in six individuals from four families (Akawi et al., 2018). A total of 20 confirmed affected individuals had been described by 2022 (Tort, 2022).

Genetic counselling
Previously described instances of HACE1mutations and SPPRS have all been inherited in an autosomal recessive manner, with phenotypically normal parents. Symptoms such as muscle dystonia and developmental delays are discovered. Prenatal testing is possible if requested by the parents, and HACE1is included in some gene panels relating to movement disorders and spasticity offered by genetic diagnostic companies.