Table 3.

Genes of Interest in the Differential Diagnosis of Nevoid Basal Cell Carcinoma Syndrome

Gene /
Genetic Mechanism		DisorderMOIFeatures of Disorder
Overlapping w/NBCCSDistinguishing from NBCCS
CYLD Brooke-Spiegler syndrome AD
  • Milia
  • BCC
  • Trichoepitheliomas & cylindromas
  • Absence of macrocephaly & other congenital & skeletal features of NBCCS
ELP1 ELP1-related pediatric medulloblastoma 1ADMedulloblastomaAbsence of macrocephaly & other congenital & skeletal features of NBCCS
GPR161 GPR161-related pediatric medulloblastoma 1, 2AD
  • Multiple BCCs
  • Medulloblastoma
  • Meningioma
  • Frontal bossing
  • Multinodular thyroid goiter
  • GI polyposis
  • GI adenoma
NSD1 Sotos syndrome AD
  • Macrocephaly
  • DD
  • Broad & prominent forehead, dolichocephaly, sparse frontotemporal hair, downslanting palpebral fissures, long & narrow face
  • Mild-to-severe ID
  • Risk of other types of tumors not reported in NBCCS
PTEN PTEN hamartoma tumor syndrome ADMacrocephaly
  • Skin features such as trichilemmoma
  • Lhermitte-Duclos disease
Xq26 duplicationBazex-Dupre-Christol syndrome (OMIM 301845)XLMultiple BCCs
  • Follicular atrophoderma on the dorsum of hands & feet, ↓ sweating, & hypotrichosis
  • Pitting on backs of hands is reminiscent of orange peel & quite unlike palmar & plantar pits of NBCCS.
  • Absence of macrocephaly & other congenital & skeletal features of NBCCS

AD = autosomal dominant; BCC = basal cell carcinoma; DD = developmental delay; GI = gastrointestinal; ID = intellectual disability; MOI = mode of inheritance; NBCCS = nevoid basal cell carcinoma syndrome; XL = X-linked

1.

Although increased risk of medulloblastoma is reported in individuals with a germline pathogenic variant in ELP1 or GPR161, the overall risks are below 1% [Smith et al 2023].

2.

One individual with a GPR161 pathogenic variant had minimal features of NBCCS; several additional individuals were only reported to have childhood-onset medulloblastoma [Begemann et al 2020].

From: Nevoid Basal Cell Carcinoma Syndrome

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