INTU and Oral-facial-digital Syndrome XVII

INTU biallelic variants underlie Oral-facial-digital Syndrome XVII, an autosomal recessive ciliopathy with characteristic craniofacial, digital, and visceral anomalies. To date, four affected individuals from three unrelated families have been reported with compound heterozygous or homozygous INTU variants in the CPLANE module (PMID:34623732). Clinical features include facial dysmorphism, high palate, tongue nodules, polydactyly, global developmental delay, brain malformations, cardiac defects, renal anomalies, and urogenital malformations (HP:0000271, HP:0000218, HP:0000199, HP:0010442, HP:0001263, HP:0001627, HP:0012210, HP:0000119) (PMID:34623732).

Genetic evidence is based on three families harboring biallelic INTU variants with autosomal recessive segregation but limited extended family data and no LOD scores. Functional data support a pathogenic mechanism via disruption of CPLANE-mediated ciliary transport, consistent with the human phenotype. No conflicting reports have emerged.

Key take-home: Biallelic INTU variants cause OFDS XVII through autosomal recessive loss of ciliary function, enabling molecular diagnosis and genetic counseling.

References

• American journal of medical genetics. Part A • 2022 • INTU-related oral-facial-digital syndrome XVII: Clinical spectrum of a rare disorder. PMID:34623732

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