Happle-Tinschert Syndrome: A Case Report of Unilateral Segmentally Arranged Basaloid Follicular Hamartoma with Scoliosis and Review of Literature

Abstract

Happle-Tinschert syndrome is a rare disease characterized by unilateral, segmentally arranged basaloid follicular hamartoma (BFH) with osseous, dental, and cerebral anomalies. Although BFH has been demonstrated to be associated with mutations in the patched gene, the genetic basis for Happle-Tinschert syndrome is still unknown. We describe a case of Happle-Tinschert syndrome in a 26-year-old female. The patient presented with unilateral skin color change to brownish papules and atrophoderma following the development of Blaschko's lines, plantar pitting, and nail dystrophy on the right side of the body. She also had scoliosis, hemihypotrophy, and dental anomalies. The skin lesions were histologically confirmed as BFHs. Next-generation sequencing of the patient's genomic DNA obtained from a peripheral blood sample identified no pathogenic mutation. This case illustrates the characteristic clinical features of Happle-Tinschert syndrome. Thus far, 14 cases of Happle-Tinschert syndrome have been reported, and we report another case of this syndrome. (Ann Dermatol 32(2) 159∼163, 2020

Molecular pathology of skin adnexal tumours

“…Molecular findings in additional follicular tumours, including basaloid follicular hamartoma and trichilemmal cysts and tumours, are shown in Tables 1 and 3 3,4,42–47 . Of note, one case of malignant proliferating trichilemmal tumour displayed an ALPK1 hot‐spot mutation identical to those described for spiradenomas (see below) 43,48 .…”

“…Molecular findings in additional follicular tumours, including basaloid follicular hamartoma and trichilemmal cysts and tumours, are shown in Tables 1 and 3. 3,4,[42][43][44][45][46][47] Of note, one case of malignant proliferating trichilemmal tumour displayed an ALPK1 hot-spot mutation identical to those described for spiradenomas (see below). 43,48 As of this writing, the molecular genetics of many follicular tumours (such as trichofolliculoma, pilar sheath acanthoma, melanocytic matricoma and tumour of the follicular infundibulum) remain undescribed.…”

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

“…These benign neoplasms of hair follicles usually manifest as skin‐colored to brownish papules 3 . Other dermatological findings include nevoid hypertrichosis or hypotrichosis, linear hyperpigmentation or hypopigmentation, linear atrophoderma, palmoplantar pitting, comedo‐like lesions, redundant skin on hands and feet, and dystrophic nails 3–6 . Reported skeletal abnormalities comprise pre‐axial or post‐axial polydactyly, saddle nose, scoliosis, deficient growth or overgrowth of limbs, cervical ribs, osteoma cutis, and abnormal bone mineralization 3–6 .…”

“…Central nervous system alterations include enlarged ventricle, optic glioma, meningioma, medulloblastoma, hemimegaloencephaly, and developmental delay 3–5 . Finally, other anomalies such as anodontia or hypodontia, enamel defects, dysplastic ears, macroglossia, conjunctival lipodermoid, microphthalmia, cataracts, epicanthus, and imperforate anus have also been reported 3–6 …”

“…3 Other dermatological findings include nevoid hypertrichosis or hypotrichosis, linear hyperpigmentation or hypopigmentation, linear atrophoderma, palmoplantar pitting, comedo-like lesions, redundant skin on hands and feet, and dystrophic nails. [3][4][5][6] Reported skeletal abnormalities comprise pre-axial or post-axial polydactyly, saddle nose, scoliosis, deficient growth or overgrowth of limbs, cervical ribs, osteoma cutis, and abnormal bone mineralization. [3][4][5][6] Central nervous system alterations include enlarged ventricle, optic glioma, meningioma, medulloblastoma, hemimegaloencephaly, and developmental delay.…”