Clinical features
Homozygous and compound heterozygous pathogenic variants in the HERC1 gene cause macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR). Patients may also have tall stature, spine abnormalities, hypotonia, seizures, behavioral problems like autism and brain structural abnormalities.
Prevalence
So far, only six patients with homozygous and compound heterozygous mutations in HERC1 (belonging to four apparently unrelated families) have been reported in the literature. Nevertheless, more individuals will likely be found as genetic testing is more commonly used for undiagnosed intellectual disability.
Diagnosis
HERC1 variants can be identified using molecular genetic testing, either by:
• Targeted sequencing of the HERC1 gene.
• Exome/genome sequencing.
Inheritance
MDFPMR is inherited in an autosomal recessive manner. To date, all patients inherited the pathogenic HERC1 variants from their (consanguineous and non- consanguineous) parents.
Recurrence risk for siblings of an affected individual is 25%. No individual with homozygous or compound heterozygous HERC1 variants has been known to reproduce.