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Ichthyosis and erythrokeratoderma v4.6 LSS Achchuthan Shanmugasundram Classified gene: LSS as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v4.6 LSS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least seven unrelated patients reported with ichthyosis and/ or erythroderma. Hence, this gene can be promoted to green rating in the next GMS update.
Ichthyosis and erythrokeratoderma v4.6 LSS Achchuthan Shanmugasundram Gene: lss has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v4.5 LSS Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: LSS.
Ichthyosis and erythrokeratoderma v4.5 LSS Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #618840) and Gene2Phenotype (LSS-related palmoplantar keratoderma-congenital alopecia syndrome with 'limited' rating on Skin panel).

The OMIM phenotype was accessed on 29 September 2025.
Ichthyosis and erythrokeratoderma v4.5 LSS Achchuthan Shanmugasundram Phenotypes for gene: LSS were changed from Alopecia-intellectual disability syndrome 4, OMIM:618840; alopecia-intellectual disability syndrome 4, MONDO:0030009 to Alopecia-intellectual disability syndrome 4, OMIM:618840; alopecia-intellectual disability syndrome 4, MONDO:0030009
Ichthyosis and erythrokeratoderma v4.4 LSS Achchuthan Shanmugasundram gene: LSS was added
gene: LSS was added to Ichthyosis and erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: LSS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSS were set to 30723320; 35830358
Phenotypes for gene: LSS were set to Alopecia-intellectual disability syndrome 4, OMIM:618840; alopecia-intellectual disability syndrome 4, MONDO:0030009
Review for gene: LSS was set to GREEN
Added comment: PMID:30723320 (2019) reported the identification of biallelic LSS variants in ten individuals from six unrelated families. In addition, one affected individual was identified with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. All 11 individuals presented with congenital alopecia and developmental delay, while ichthyosis and/ or erythroderma were found in eight of these individuals from six families.

PMID:35830358 (2022) reported a 4-day-old female patient who presented with alopecia and a previously unreported dermatologic manifestation of congenital localized hyperpigmentation. Examination of the patient also revealed features consistent with ichthyosis. The patient was identified with two variants in LSS gene and a de novo pathogenic variant in SPTAN1 gene. The SPTAN1 variant is associated with neurodevelopmental phenotypes including early infantile epileptic encephalopathy. There are no known cutaneous manifestations of SPTAN1 variant.
Sources: Literature