Segmentally Arranged Basaloid Follicular Hamartomas with Osseous, Dental and Cerebral Anomalies: A Distinct Syndrome

Abstract

A 39-year-old man presented with multiple basaloid follicular hamartomas involving the right side of his body in a systematized pattern following Blaschko’s lines. His right leg was 22.5 cm shorter than the left, and rudimentary pre-axial polydactyly was noted on the left hand and the right foot. The teeth of the right maxilla were hypoplastic. DNA analysis of blood lymphocytes and fibroblasts from lesional skin did not reveal any mutation in the Patched gene. On account of this case and of 8 similar cases found in th e literature, the spectrum of a distinct syndrome is delineated. Ipsilateral extracutaneous defects include cervical ribs, polydactyly, malformed thumb and disproportionate overgrowth or deficient growth of limb bones; dental anomalies in the form of anodontia, hypodontia or ameloblastoma; and cerebral defects such as mental retardation, unsteady gait, meningioma and optic glioma. The cutaneous lesions of this syndrome should not be called “basal cell naevus” as this will lead to continuing confusion with Gorlin syndrome. The molecular basis of the disorder remains to be elucidated.

Happle‐Tinschert syndrome variable phenotype as part of the mosaic hedgehog spectrum: Report of three cases

“…Based on this case and eight similar cases previously reported under different designations (unilateral skin lesions associated with multiple neoplasms, nevus comedonicus syndrome, and unilateral linear basal cell and adnexal nevus), they defined the spectrum of a distinct syndrome. 1 The authors concluded that the syndrome represented a mosaic phenotype. Later that same year, Itin reported another similar case and proposed the term Happle-Tinschert syndrome.…”

Segmental basaloid follicular hamartomas derive from a post‐zygotic SMO p.L412F pathogenic variant and express hair follicle development‐related proteins in a pattern that distinguish them from basal cell carcinomas

“…Lesions present at birth, during childhood or puberty (López Jiménez et al, 2017). Segmental BFH can occur in association with systemic manifestations in Happle‐Tinschert syndrome (HTS), a mosaic disorder characterized by segmental BFH along with skeletal, ophthalmic, and other systemic abnormalities (Happle & Tinschert, 2008, 2016; Lovgren et al, 2020). This syndrome phenotypically overlaps with Curry‐Jones syndrome (CJS; OMIM 601707) found in 2016 to be caused by a recurrent post‐zygotic SMO , c.1234C>T, p.L412F pathogenic variant (Twigg et al, 2016).…”