Main clinical features
The PCH10 caused by mutations in the CLP1 gene is a neurologic disorder characterized by poor growth (body weight, length and head size), delay or absence of motor skills including head control, sitting, walking, and speaking, intellectual disability, and epilepsy.
Genetic background, inheritance and genetic counseling
All reported patients had the same single nucleotide change in DNA sequence at homozygous state, suggesting autosomal recessive inheritance and a founder affect which means that this DNA sequence change originates from a common ancestor. Given the autosomal recessive inheritance pattern, the parents of an affected child are obligate heterozygotes (i.e., carriers of one pathogenic variant) and they don’t have the risk of developing the disease. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier (like parents), and a 25% chance of being unaffected and not a carrier. Once the CLP1 pathogenic variant(s) have been identified in an affected individual, prenatal testing for any future pregnancy of the mother at increased risk and preimplantation genetic diagnosis are possible.