Ichthyosis and erythrokeratoderma

Gene: LSS

Green List (high evidence)

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.

Created: 29 Sep 2025, 9:29 p.m. | Last Modified: 29 Sep 2025, 9:29 p.m.

Panel Version: 4.6

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.

Created: 29 Sep 2025, 9:28 p.m. | Last Modified: 29 Sep 2025, 9:28 p.m.

Panel Version: 4.5

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

Created: 29 Sep 2025, 9:26 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alopecia-intellectual disability syndrome 4, OMIM:618840; alopecia-intellectual disability syndrome 4, MONDO:0030009

Publications

• 30723320
• 35830358