Pigmentary skin disorders

Gene: SMARCB1

I don't know

Comment on list classification: Since cafe-au-lait or other pigmentary changes do not appear to be common in Schwannomatosis-1, or the presenting feature, this gene has been rated red on this panel.

Created: 17 Jun 2025, 10:16 p.m. | Last Modified: 17 Jun 2025, 10:17 p.m.

Panel Version: 4.3

SMARCB1 is associated with several disorders in OMIM including {Schwannomatosis-1, susceptibility to} OMIM:162091 (AD). Schwannomas are benign tumours of the peripheral nervous system. It appears that in somatic tumour cells there can be a 'second hit' in the same or another gene e.g. PMID: 17357086, PMID: 17357086.

Gene reviews for LZTR1- and SMARCB1-Related Schwannomatosis (https://www.ncbi.nlm.nih.gov/books/NBK487394/, last reviewed Apr 2024) states that "Cutaneous manifestations including café au lait macules, skin fold freckling, and cutaneous schwannomas typical of other forms of neurofibromatosis are not common features of LZTR1- or SMARCB1-related schwannomatosis."

PMID: 19124645 - Swensen et al 2009 - In a family with a four generation history of MRT predisposition and schwannomatosis a duplication of exon 6 of SMARCB1 was identified. NO café-au-lait macules, axillary or inguinal freckling, or other pigmentary changes were detected in the 5 examined affected family members.

PubMed: 19582488 - Bacci et al 2010 - 4 individuals in an Italian family with multiple schwannomas and meninigiomas with a missense variant in SMARCB1. 1/4 individuals are reported to have cafe-au-lait spots but the presenting feature was multiple peripheral schwannomas.

PMID: 17357086 - Hulsebos et al 2007 - 2 members of a family are reported to have multiple schwannomas were found to have germline variant in INI1/SMARCB1 predicted to result in a stop codon. Only SMARCB1 was sequenced. Analysis of a schwannoma in the father revealed a second variant predicted to result in a premature stop codon. No skin pigmentary changes were reported.

Created: 17 Jun 2025, 10:15 p.m. | Last Modified: 17 Jun 2025, 10:15 p.m.

Panel Version: 4.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

Included in the review PMID: 32972601 as differential for cafe-au-lait
Sources: Expert Review

Created: 23 Apr 2024, 8:46 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Schwannomatosis-1, susceptibility to

Publications

• PMID: 32972601