ZNF699 – DEGCAGS syndrome

ZNF699-related DEGCAGS syndrome is an autosomal recessive disorder characterized by developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities. A consanguineous Middle Eastern family presented an infant with in utero growth restriction, premature labor, breech presentation, hypotension, bradycardia, generalized hypotonia, facial dysmorphia, and multi‐system involvement including ocular abnormalities (PMID:38014480). The proband was homozygous for a novel missense variant c.1379C>T (p.Ser460Leu) in ZNF699, confirming molecular diagnosis (PMID:38014480). This represents the 15th reported individual with DEGCAGS syndrome and the first with a homozygous ZNF699 missense change. Segregation analysis identified one additional affected sibling with severe neonatal hypotonia and chronic ventilator dependence, supporting pathogenicity in a recessive model.

To date, all reported cases share biallelic ZNF699 variants, though functional studies on ZNF699 are lacking. No experimental assays or animal models have evaluated the impact of ZNF699 deficiency on developmental pathways in DEGCAGS. Additional reports and functional characterization are required to elucidate molecular mechanisms. Nevertheless, ZNF699 sequencing in infants with hypotonia, cardiovascular instability, and multisystem anomalies provides definitive diagnosis, informs recurrence risk, and guides multidisciplinary management.

References

• Molecular Genetics & Genomic Medicine • 2024 • Clinical and ocular abnormalities in DEGCAGS syndrome-Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities. PMID:38014480

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