Beyond the Surface: Clinical and genetic insights in CEDNIK Syndrome

CEDNIK Syndrome, caused by loss-of-function mutations in the SNAP29 gene, exemplifies the intricate relationship between genetic abnormalities and their diverse clinical manifestations. This rare neurocutaneous syndrome was first described in 2005 and is characterized by cerebral dysgenesis, developmental delay, neuropathy, and skin changes such as ichthyosis and palmoplantar keratoderma [1]. Fewer than 25 cases have been reported globally, with only four documented from India [2,3,4, 5]. This case adds valuable insights by identifying a homozygous SNAP29 mutation (Chr22: g.20881101_20881102dup), which led to premature truncation of the SNAP29 protein, confirming the diagnosis.

The clinical features observed in this patient align with the previously described phenotypic spectrum of CEDNIK Syndrome. Dysmorphic features, ichthyosis, and global developmental delays are hallmark findings that reflect the critical role of SNAP29 in cellular trafficking, epidermal differentiation, and neural development [6, 7]. Imaging abnormalities, including partial agenesis of the corpus callosum and white matter changes, are diagnostic hallmarks [8]. These findings were consistent with reports by Sprecher et al. and Mah-Som et al., which documented similar neuroimaging anomalies including cortical dysplasia, as well as hypomyelination, white matter loss, and white matter signal anomalies suggestive of a leukodystrophy [8]. Importantly, this case also highlights antenatal findings, such as oligohydramnios and cerebral ventricular dilatation, which may serve as early clues in affected pregnancies.

Whole exome sequencing played a pivotal role in this diagnosis, emphasizing the importance of genetic testing in rare syndromes. Genetic counselling was crucial for the family, especially in the context of a consanguineous marriage, to provide information on recurrence risks and future reproductive options [4,7]. This underscores the significance of genetic evaluation in regions with a high prevalence of consanguinity, where rare autosomal recessive conditions are more frequently observed [6,8].

Management of CEDNIK Syndrome remains supportive, as no curative treatment exists, and expected lifespan is short, [7, 8] with most patients not surviving beyond the second decade, with the oldest patient reported as nineteen years of age. [8]. Early intervention with physical therapy, speech therapy, and multidisciplinary care can optimize developmental outcomes [5,6]. Dermatological management is equally essential, given the progressive nature of palmoplantar keratoderma and ichthyosis [9]. Mah-Som et al. have highlighted the limited life expectancy in CEDNIK Syndrome, with most patients not surviving beyond the second decade of life, emphasizing the importance of proactive and symptomatic management [6,7].

This report contributes to the growing body of literature on CEDNIK Syndrome, particularly in expanding the genotypic and phenotypic spectrum. By documenting this case in an Indian patient, it highlights the importance of awareness among clinicians, especially in resource-limited settings, to ensure timely diagnosis and comprehensive care. Increased vigilance and collaboration among paediatricians, dermatologists, neurologists, and geneticists are critical to improving outcomes and providing holistic care for affected individuals and their families [8, 9, 10].