Happle-Tinschert Syndrome

Abstract

Recently, Happle and Tinschert [Acta Derm Venereol 2008;88:382–387] described the case of a multisystem birth defect with segmentally arranged basaloid follicular hamartomas associated with extracutaneous defects in the form of short leg, polydactyly and hypoplastic teeth. The authors presented a comprehensive overview of 8 similar cases reported under various designations, and provided evidence that this syndrome includes various additional defects of the bones, teeth and brain. Here, a further typical case is reported, and it is emphasized that this phenotype should no longer be categorized as ‘basal cell nevus syndrome’, and thus be confused with the nevoid basal cell carcinoma syndrome of Gorlin [Cancer 1965;18:89–104]. A 7-year-old boy had multiple whitish and some scattered brownish basaloid follicular hamartomas involving the right side of his body in a systematized pattern following the lines of Blaschko. These lesions had been present since birth. They were hairless and conspicuously hypopigmented. In addition, enamel defects and mild webbing of the first and second right toes were noted. At the age of 5 years, the boy developed a medulloblastoma that originated from the ipsilateral paramedian vermis region. The tumor was surgically removed, and subsequently radiotherapy and chemotherapy were applied. Analysis of blood DNA did not reveal any Patched mutation. The molecular basis of the disorder remains to be elucidated. From this case and from 9 similar cases reported in the literature, the spectrum of a distinct phenotype is delineated, and the eponymic designation Happle-Tinschert syndrome is proposed.

Happle-Tinschert Syndrome: Report of a Case with Hemimegalencephaly

“…The main cutaneous finding of this disease is the presence of unilateral segmentally arranged basaloid follicular hamartomas. Associated abnormalities reported so far in Happle-Tinschert syndrome are skeletal findings (disproportionate overgrowth or deficient growth of limb bones, scoliosis, widening of ribs, rudimentary ribs, polidactyly, syndactyly, malformed thumb, socket-type or saddle nose, frontal bossing, abnormal bone mineralization, ipsilateral premature closure of epiphyses), dental pathologies (anodontia, hypodontia, enamel defects), cerebral anomalies (mental retardation, unsteady gait, enlarged ventricle, ipsilateral hemiplegia, mild hemimegalencephaly) and other disorders such as microphtalmia, coloboma of optic nerve, cataract or an imperforate anus (1, 2, 3). In addition, ipsilateral tumors appear to have an increased incidence; medulloblastoma, optic glioma, menengioma, ameloblastoma of the mandible and colonic adenocarcinoma have been reported in patients with Happle-Tinschert syndrome (1, 2, 3).…”

“…On the other hand, the herein described hemimegalencephaly is an unknown feature of Gorlin syndrome. Although a case with medulloblastoma was presented in a patient with Happle-Tinschert syndrome (2), an increased incidence of medulloblastoma is actually a feature of Gorlin syndrome. These tumors usually occur within the first 2 years of life in Gorlin syndrome (6).…”

“…They stated this disease as a distinct syndrome which has been confused with Gorlin syndrome in the past. Shortly after this article, Itin (2) reported a new case with similar features. He described the disease as 'segmentally arranged basaloid follicular hamartomas, linear atrophoderma with hypo- and hyperpigmentation, enamel defects, ipsilateral hypertrichosis, and skeletal and cerebral anomalies' and proposed the name 'Happle-Tinschert syndrome'.…”

Varied Malignant presentations in a single case of xeroderma pigmentos

“…Two important causes of mortality are metastatic malignant melanoma and squamous cell carcinoma [7]. Patients younger than 20 years have a 1000-fold increase in the incidence of non melanoma skin cancer and melanoma [8]. The mean patient age for the development of skin cancer is 8 years in the patients with XP compared to 60 years in the healthy population.…”

Segmental Acne versus Mosaic Conditions with Acne Lesions

“…Segmentally arranged basaloid follicular hamartomas in the setting of Happle-Tinschert syndrome, whose main features include linear atrophoderma with hypo- and hyperpigmentation, enamel defects, ipsilateral hypertrichosis, and skeletal and cerebral anomalies [30,31], may often show comedo-like plugs. This syndrome includes all the (few) cases previously reported as ‘linear unilateral basal cell nevus with comedones’.…”