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Background: Two loci (CHD7 and SOX10) underlying Kallmann syndrome (KS) were discovered through clinical and genetic analysis of CHARGE and Waardenburg syndromes, conditions that include congenital anosmia caused by olfactory bulb (CA/OBs) defects and congenital hypogonadotropic hypogonadism (CHH). We hypothesized that other candidate genes for KS could be discovered by analyzing rare syndromes presenting with these signs. Study Design, Size, Duration: We first investigated a family with Gorlin-Goltz syndrome (GGS) in which affected members exhibited clinical signs suggesting KS. Participants/Materials, Methods: Proband and family members underwent detailed clinical assessment. The proband received detailed neuroendocrine evaluation. Genetic analyses included sequencing the PTCH1 gene at diagnosis, followed by exome analyses of causative or candidate KS/CHH genes, in order to exclude contribution to the phenotypes of additional mutations. Exome analyses in additional 124 patients with KS/CHH probands with no additional GGS signs., Results: The proband exhibited CA, absent OBs on magnetic resonance imaging, and had CHH with unilateral cryptorchidism, consistent with KS. Pulsatile Gonadotropin-releasing hormone (GnRH) therapy normalized serum gonadotropins and increased testosterone levels, supporting GnRH deficiency. Genetic studies revealed 3 affected family members harbor a novel mutation of PTCH1 (c.838G> T; p.Glu280*). This unreported nonsense deleterious mutation results in either a putative truncated Ptch1 protein or in an absence of translated Ptch1 protein related to nonsense mediated messenger RNA decay. This heterozygous mutation cosegregates in the pedigree with GGS and CA with OBs aplasia/hypoplasia and with CHH in the proband suggesting a genetic linkage and an autosomal dominant mode of inheritance. No pathogenic rare variants in other KS/CHH genes cosegregated with these phenotypes. In additional 124 KS/CHH patients, 3 additional heterozygous, rare missense variants were found and predicted in silico to be damaging: p.Ser1203Arg, p.Arg1192Ser, and p.Ile108Met., Conclusion: This family suggests that the 2 main signs of KS can be included in GGS associated with PTCH1 mutations. Our data combined with mice models suggest that PTCH1 could be a novel candidate gene for KS/CHH and reinforce the role of the Hedgehog signaling pathway in pathophysiology of KS and GnRH neuron migration., (© 2020 S. Karger AG, Basel.)

Background: Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin-Goltz syndrome) presents various symptoms and can disfigure patients. The estimated prevalence is around 1:100,000., Objective: To systematically investigate the clinical manifestations of NBCCS patients of the Zurich register and compare them with those described in 4 epidemiological studies performed in other countries., Methods: We analyzed patient characteristics and clinical manifestations in a register of 30 NBCCS patients in Zurich, Switzerland. We compared our findings to the results of 4 epidemiological studies performed in America, Australia, Japan and the UK., Results: We obtained information concerning basal cell carcinomas (BCCs) and jaw cysts from 28 patients out of our population of 30 NBCCS patients. The mean age at onset of the first BCC was 24 years, and the mean age at diagnosis of the first jaw cyst was 15.6 years. The average number of jaw cysts was 8.4; the average number of BCCs was 207. 72.5% of the examined BCCs showed a nodular histology, but we also found scirrhous and superficial types., Conclusion: The disease burden associated with NBCCS diagnosed in Swiss patients is significant and comparable to that of other countries. Regular skin examination and oromaxillary examinations should be performed early in diagnosis, and patients should undergo early UV protection. Nodular BCC is the most common BCC subtype in this patient population., (© 2016 S. Karger AG, Basel.)

Background: Gorlin syndrome is a rare autosomal-dominant disorder characterized by a wide range of developmental abnormalities and various tumors. The syndrome is caused by mutations in PTCH1, a tumor suppressor gene located at 9q22.32. We describe a Gorlin syndrome case with typical features of the syndrome and no mutations in PTCH1, but with a large deletion of the 9q22 region that has rarely been described., Objective: To fully characterize the large deletion in the patient., Methods: In order to map the size and position of the deletion, we developed quantitative multiplex fluorescent PCR with polymorphic markers surrounding the PTCH1 gene, followed by long-range PCR and sequencing., Results: The deleted segment of 4.5 Mb in the 9q22.32-q22.33 region was determined, and included the entire PTCH1, its promoter and 22 OMIM genes., Conclusion: We suggest that screening for large deletions should be included in standard mutation screening for Gorlin syndrome patients., (Copyright 2009 S. Karger AG, Basel.)

Background: The naevoid basal cell carcinoma syndrome (NBCCS) is a therapeutic challenge due to the multiplicity of cutaneous tumours. Photodynamic therapy (PDT) is increasingly used as an alternative treatment for superficial and in some countries nodular basal cell carcinomas (BCC)., Objective: To study the safety and efficiency of PDT in NBCCS., Methods: We reviewed retrospectively the evolution of 62 lesions from patients with multiple BCC treated with PDT., Results: The initial response rate (85.4%, 53/62) and recurrence rate (7.5%) appeared comparable to literature values in NBCCS and to those reported in the treatment of sporadic BCC. The clearance rate without recurrence was 79% (49/62), during a mean follow-up period of 13 months. The cosmetic outcome was excellent. Recurrences were found almost 2 years after treatment., Conclusion: PDT is a suitable therapeutic option in the management of NBCCS patients but requires a strict and long follow-up., (Copyright 2009 S. Karger AG, Basel.)

Focal dermal hypoplasia is a syndrome characterized by anomalies of cutaneous, osseous, dental and ocular structures. Because of the ocular anomalies, this syndrome should be regarded as a fifth type of phakomatosis. The differences between the fibroblasts obtained from skin lesions and fibroblasts obtained from normal skin and controls could be the demonstration of mosaicism and the consequence of lyonization. The authors present the case of a baby with typical anomalies of the Gorlin-Goltz syndrome and abnormal growth characteristics of skin fibroblasts.

A girl with unilateral partly depigmented, partly hyperpigmented atrophic skin lesions, hypertrichosis, postauricular nodules, cataracts, and mild mental retardation is presented. Additionally, she developed multiple neoplasms as optic glaucoma, a psammomatous meningioma and an ameloblastoma. It remains unclear whether our patient suffers from a variant of the epidermal nevus syndrome or a new neuro-ectodermal dysplasia.

A patient is reported with the basal cell nevus syndrome (BCNS) in combination with a webbed neck. This symptom might be considered as an expression of the BCNS.