Ectodermal dysplasia

Gene: LSS

Green List (high evidence)

Comment on list classification: As reviewed by Eleanor Williams, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 29 Sep 2025, 10:10 p.m. | Last Modified: 29 Sep 2025, 10:10 p.m.

Panel Version: 4.6

Comment on phenotypes: This gene has been associated with relevant phenotypes in both OMIM (MIMs #618275 & #618840) and Gene2Phenotype (LSS-related hypotrichosis & LSS-related palmoplantar keratoderma-congenital alopecia syndrome with 'limited' rating on Skin panel).

OMIM phenotypes have been last accessed on 29 September 2025.

Created: 29 Sep 2025, 10:08 p.m. | Last Modified: 29 Sep 2025, 10:08 p.m.

Panel Version: 4.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alopecia-intellectual disability syndrome 4, OMIM:618840; alopecia-intellectual disability syndrome 4, MONDO:0030009; Hypotrichosis 14, OMIM:618275; hypotrichosis 14, MONDO:0032649

Green List (high evidence)

Comment on list classification: Promoting this gene from red to amber for now, but with a recommendation for consideration for a green rating following GMS review, if appropriate for the panel.

Created: 12 Jan 2021, 10:06 p.m. | Last Modified: 12 Jan 2021, 10:06 p.m.

Panel Version: 1.15

Associated with Hypotrichosis 14 618275 (AR) in OMIM.

PMID: 32101538 - Wada et al 2020 - report two siblings from a nonconsanguineous Japanese family with novel biallelic LSS mutations (compound het) who presented congenital hypotrichosis, midline anomalies, such as cleft palate and agenesis of the corpus callosum, and no cataracts. The motor and mental development of the patients were normal. They also created tissue specific knock-out mice as Lss constitutive knockout mice are embryonically lethal, and found epidermis-specific knockout of Lss caused hypotrichosis, lens-specific Lss knockout mice had cataracts.

PMID: 30723320 - Besnard et al 2019 - report 7 unrelated families (11 individuals) with variants in LSS who present with alopecia (11/11), intellectual disability (10 mod/severe, 1 mild) and epilepsy (7/11). Segregation data shown for 6 families.

PMID: 30401459 - Romano et al 2018 - report 3 unrelated (Arabic, Swiss, Afgan origin) families with potentially autosomal-recessive Hypotrichosis simplex in which they identify by WES 5 five different missense and nonsense mutations in LSS. Variants were shown to segregate with the disorder in 2 families (DNA not available for the third). In one family the siblings also presented with intellectual disability but the authors consider this coincidental. No other phenotypes such as cataracts were reported.

PMID: 29016354 - Chen and Lui 2017 - report a pediatric patient with congenital cataract, small penis, baldness and absence of eyebrows and compound heterozygous variants in LSS.
Sources: Literature

Created: 12 Jan 2021, 10:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypotrichosis 14 OMIM:618275; hypotrichosis 14 MONDO:0032649

Publications

• 32101538
• 30401459
• 30723320
• 29016354