Hypoparathyroidism-Retardation-Dysmorphism Syndrome (TBCE)
Hypoparathyroidism-retardation-dysmorphism syndrome (HRDS), also known as Sanjad-Sakati syndrome, is an autosomal recessive disorder caused by pathogenic variants in the gene TBCE. HRDS is characterized by intrauterine and postnatal growth retardation, infantile hypoparathyroidism, seizures, facial dysmorphism and developmental delay. Pathogenic variants in TBCE can also cause two other rare disorders:
- Kenney-Caffey syndrome, type 1 is an autosomal recessive disorder with childhood onset that has a phenotype similar to HRDS, but includes impaired skeletal development with small and dense bones and recurrent bacterial infections.
- Progressive encephalopathy with amyotrophy and optic atrophy (PEAMO) is an autosomal recessive neurodegenerative disorder with infantile onset. PEAMO is characterized by developmental delay and hypotonia which progresses to regression of motor skills, distal amyotrophy of all four limbs and spastic tetraplegia. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy.
A limited genotype-phenotype relationship has been reported, due to the presence of several pathogenic founder variants. Life expectancy of the affected individuals depends on the severity of the clinical manifestations.
For information about carrier frequency and residual risk, please see the residual risk table.