Adult‐Onset CTC1 ‐Related Disorder With Kidney Disease, Subcutaneous Dystrophic Calcifications and Telomere Length Conservation

Résumé fourni par la source

Biallelic pathogenic variants in the CTC1 gene are associated with cerebroretinal microangiopathy with calcifications and cysts (CRMCCs), also known as Coats plus syndrome (CPS; OMIM #612199). This rare multisystem condition is characterized by early childhood onset of intracranial calcifications, leukodystrophy and cysts, along with retinal telangiectasia and exudates (Coats disease). We report a woman referred to genetics with complex multisystem clinical manifestations beginning in her 30s and progressing over two decades. In keeping with classical features of the condition, she presented a complex medical history of pathological bone fractures, gastrointestinal ectasias, and premature aging. In addition, she developed progressive thrombotic microangiopathy-associated kidney disease requiring transplantation, suspected liver cirrhosis, and subcutaneous dystrophic calcifications. Exome sequencing identified compound heterozygous likely pathogenic variants in CTC1, consisting of a previously reported missense variant and a novel truncating variant confirmed in trans. Despite clinical features suggestive of premature aging, telomere length analysis demonstrated low-normal values for age, supporting emerging evidence that telomere shortening is not a consistent feature of CTC1-related disorders. This case represents the second confirmed adult-onset CTC1-related disorder and the longest survival to date. The findings suggest that subcutaneous calcifications and progressive renal and multi-organ disease may represent later-onset manifestations of the condition. TMA may be a pathologic feature of the multi-system impacts of this rare disease in adults.

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