Dominant ELOVL1‐Related Ichthyotic Keratoderma (IKSHD) in an Adult: Preserved Cognition With Functional Autonomy and Epilepsy

Ichthyotic keratoderma with spasticity, hypomyelination and dysmorphic features (IKSHD; OMIM #618527) is an ultra‐rare neuroichthyosis caused by dominant variants in ELOVL1, the elongase of very‐long‐chain fatty acids required for both the epidermal permeability barrier and central nervous system myelin. The recurrent variant c.494 C > T, p.(Ser165Phe) has, to date, been reported in only three patients, all children or adolescents. A feature that distinguishes IKSHD from ELOVL4‐related ISQMR (ichthyosis, spastic quadriplegia and intellectual disability) is the preservation of intellect; whether this is maintained beyond childhood has been unknown. We describe a 28‐year‐old man, the fourth reported patient with this variant and the first adult, with life‐long generalized ichthyosiform scaling and pruritus, together with a severe spastic‐ataxic tetraparesis, dysarthria, pendular nystagmus and childhood‐onset epilepsy. Skin biopsy showed compact orthohyperkeratosis with focal parakeratosis and scattered cytoid bodies, and molecular testing confirmed the heterozygous pathogenic ELOVL1 variant. Serial brain MRI over 13 years demonstrated a qualitatively stable, parieto‐occipital‐predominant periventricular leukoencephalopathy. Despite profound motor disability, cognition was fully preserved: he completed a university degree and lives independently with personal assistance. Topical calcipotriol and emollients improved the cutaneous scaling and pruritus, while dupilumab is held in reserve. This case documents the natural history of dominant ELOVL1 disease into adulthood, shows that its characteristic sparing of intellect endures and translates into meaningful functional autonomy, and broadens the neurological phenotype to include epilepsy. The stability of the leukoencephalopathy over more than a decade suggests a largely developmental, non‐progressive myelin deficit.