Congenital Cataract Facial Dysmorphism Neuropathy Syndrome, CCFDN - CTDP1

CTDP1

Klinische Symptomatik

Congenital Cataract Facial Dysmorphism Neuropathy Syndrome (CCFDN Syndrome) is a rare autosomal recessive disease that has thus far only been described for the Roma population. Affected patients exhibit a complex clinical phenotype involving multiple organs. This includes congenital cataracts, microcorneae, hypomyelinating peripheral neuropathy, dwarfism, facial dysmorphism, and delayed psychomotor development. Parainfectious rhabdomyolysis can become a serious complication; the risk of complications under general anaesthesia is also heightened. Cataract surgery is recommended early on in order to prevent long-lasting impairment of vision.

Genetik

CCFDN Syndrome is caused by a mutation in the CTDP1 gene (C-terminal domain of RNA Polymerase II subunit A) located on chromosome 18q23. The known mutation is an intronic founder mutation (c.863+389 C>T, Leu287fs) in intron 6.

RT-PCR and sequence analysis has revealed the rare mechanism of aberrant splicing. The donor site created by a C>T transition activates a cryptic acceptor site located upstream, through which 95 nucleotides in an alu element are inserted into the processed CTDP1 mRNA.

CCFDN Syndrome follows an autosomal recessive pattern of inheritance.

Häufigkeit

Rare, though common among Roma.

 

Diagnostik