Goltz-Gorlin syndrome is a rare X-linked inherited disorder associated with PORCN (porcupine homolog-Drosophila) gene mutation. It primarily affects the skin and its appendages. The characteristic cutaneous features include a blaschko-linear pattern, skin atrophy, pigmentary changes, and telangiectasia. The oral manifestations have been reported in more than half of the affected individuals. The most common oral findings include enamel hypoplasia, hypodontia, supernumerary teeth, microdontia, vertical grooving of the teeth, taurodontism, fusion, and abnormal root morphology reported in sporadic cases. The objective of this case report is to describe the dentofacial characteristics of a middle childhood aged girl with Goltz-Gorlin syndrome.

BACKGROUND: The diagnostic process for children and adults manifesting a constellation of ectodermal abnormalities requires a conscientious and highly structured process.
METHODS: Six girls (aged 6-month-8 years) and two older girls (aged 13 and 16 years) were born with variable skin lesions of varying intensities associated with noticeable cranial and skeletal malformation complexes. Cleft palate, abnormal dentition, and multiple papillomas were evident around the mouth, mostly bilateral but asymmetrical in the upper and lower limbs. Exaggerated frontal bossing (macrocephaly) and in some patients\' microcephaly with variable skeletal defects of the craniocervical junction and diverse forms of lower limb deformities of syndactyly, polydactyly, and split-hand/foot (ectrodactyly).
RESULTS: All patients manifested the constellation of abnormalities with variable intensities ranging between alopecia, papillomas, striated skin pigmentations split-hand/foot (ectrodactyly), and major bone defects. A 3D reconstruction CT scan was directed mainly to further scrutinize children with pseudo cleft lip, submucus cleft, and cleft palate. Interstingly, they manifested massive demineralization of the cranium associated with severely defective dentition. A spine 3D reconstruction CT scan in two girls showed marked cystic cavitation of the upper jaw associated with excessive cavitation of the mastoid, causing tremendous frailty of the mastoid bone. A 3D sagittal CT scan showed odontoid hypoplasia and C1-2 instability associated with the rudimentary atlas and the persistence of extensive synchondrosis of the cervico-thoracic spine. The overall clinical and radiological phenotypic characterizations were consistent with the diagnosis of focal dermal hypoplasia (Goltz syndrome). Two children manifested heterozygous mutations in the PORCN gene, chromosome Xp11.
CONCLUSIONS: In this study, we believe it\'s a good opportunity to share our novel scientific findings, which are intriguing and can be inspiring to readers, and to further aid the current scientific literature with exceptionally new unveiling results. This is the first comprehensive study of the cranio-skeletal malformation complex in children with GS.

Goltz-Gorlin syndrome (GGS), also known as focal dermal hypoplasia, is a rare X-linked disorder caused by pathogenic variants in the PORCN gene and characterized by several abnormalities, including skin and limb defects, papillomas in multiple organs, ocular malformations, and mild facial dysmorphism. To date, only approximately 300 cases have been described in the literature. A 16-year-old female patient, born with multiple congenital dysmorphisms consistent with GGS and confirmed by genetic exam, was referred to our outpatient clinic for the workup of a thyroid nodule. A thyroid ultrasound showed a bilateral nodular disease with a 17-mm large hypoechoic nodule in the right lobe. Cytological exam of fine needle aspiration biopsy was suspicious for malignancy. Thus, she underwent total thyroidectomy plus lymphadenectomy of the right central compartment. A histological exam disclosed a papillary thyroid carcinoma (PTC) with lymph node micrometastases. Radioiodine (131-Iodine) therapy was performed. At 3- and 6-month follow-up, the patient did not present either ultrasound or laboratory PTC recurrence. To our knowledge, we report the first case of PTC in a patient with GGS. Since thyroid cancer is rare among children and adolescents, we hypothesize that the PORCN pathogenic variant could be responsible for tumor susceptibility. We also provide an overview of the clinical findings on GGS patients already reported and discuss the possible pathogenetic mechanism that may underlie this rare condition, including the role of PORCN in tumor susceptibility.

Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare syndrome described in the literature. Patchy skin hypoplasia is the most evident sign. Hyperpigmentation, hypopigmentation, papillomas, limb defects, and orofacial manifestations have also been reported. A 12-year-old Saudi girl with unremarkable family history presented with FDH. The diagnosis was confirmed using a genetic study. Physical examination revealed asymmetrical streaks of vermiculate dermal atrophy, telangiectasia with hyperpigmentation, and hypopigmentation on the left half of the face, trunk, and bilateral extremities. It appears along Blashko lines. No mental impairment was observed. Intraoral examination generalized plaque-induced gingivitis with erythematous gingival hyperplasia. Examination of the teeth showed generalized enamel hypoplasia with abnormal tooth formations, malalignment, microdontia, spacing and tilting, and minimal caries. As reported cases of FDH are rare worldwide, this syndrome is yet to be fully understood. As the manifestation of the syndrome varies among cases, the management of each case is unique. This emphasizes the importance of reporting cases of FDH.

UNASSIGNED: Focal dermal hypoplasia (Goltz syndrome) is a genetic multisystem disorder characterized primarily by involvement of the skin associated to face, skeletal, and eyes anomalies. The objective of the present series is to shed light on this rare syndrome and these atypical manifestations.
UNASSIGNED: Our study reports the case of five Moroccan patients who present typical clinical picture of the Goltz syndrome with some rare manifestations.
UNASSIGNED: A total of 5 patients with Goltz syndrome were evaluated. All of them are female with one familial case. The age ranged from 8 months to 35 years. A characteristic Blaschkoid hypo- and hyper-pigmented skin lesions, congenital nodular fat herniation, and skin atrophy were present in all patients. Ocular manifestations were present in 80% of patients. Cranio-facial deformity was seen in 80% of patients. Short stature and intellectual delay were documented in 80% and 40% of patients, respectively. Limb abnormality was found in all patients. Two patients had a cleft lip, one of which unusual lateral facial cleft.
UNASSIGNED: Genetic testing could not be performed in the present series.
UNASSIGNED: Through this work we will discuss the different clinical signs and genetic aspects of Goltz syndrome and the interest of a good clinical expertise.

暂无摘要。

Microphthalmia, anophthalmia, and coloboma (MAC) are congenital ocular malformations causing 25% of childhood blindness. The X-linked disorder Focal Dermal Hypoplasia (FDH) is frequently associated with MAC and results from mutations in Porcn, a membrane bound O-acyl transferase required for palmitoylation of Wnts to activate multiple Wnt-dependent pathways. Wnt/β-catenin signaling is suppressed in the anterior neural plate for initiation of eye formation and is subsequently required during differentiation of the retinal pigment epithelium (RPE). Non-canonical Wnts are critical for early eye formation in frog and zebrafish. However, it is unclear whether this also applies to mammals. We performed ubiquitous conditional inactivation of Porcn in mouse around the eye field stage. In Porcn CKO , optic vesicles (OV) arrest in growth and fail to form an optic cup. Ventral proliferation is significantly decreased in the mutant OV, with a concomitant increase in apoptotic cell death. While pan-ocular transcription factors such as PAX6, SIX3, LHX2, and PAX2 are present, indicative of maintenance of OV identity, regional expression of VSX2, MITF, OTX2, and NR2F2 is downregulated. Failure of RPE differentiation in Porcn CKO is consistent with downregulation of the Wnt/β-catenin effector LEF1, starting around 2.5 days after inactivation. This suggests that Porcn inactivation affects signaling later than a potential requirement for Wnts to promote eye field formation. Altogether, our data shows a novel requirement for Porcn in regulating growth and morphogenesis of the OV, likely by controlling proliferation and survival. In FDH patients with ocular manifestations, growth deficiency during early ocular morphogenesis may be the underlying cause for microphthalmia.

UNASSIGNED: Focal dermal hypoplasia is a genetic disease of multiple systems initially affecting the skin, skeleton, dental, eyes and face with developmental abnormalities and facial dysmorphism. Focal dermal hypoplasia is X-linked dominant disease affecting the ectoderm, mesoderm and endoderm. 95% feature de novo and 90% of these are females. Focal dermal hypoplasia is induced by a mutation in the PORCN gene.
UNASSIGNED: The aim of this article is to present a case of a one-year-old girl child with multi-hypopigmented reticulated atrophic macules and patches grouped in linear mode at the lines of blaschko, skeleton abnormalities, umbilical hernia, developmental delay, hypoplastic nails, syndactyly and lobster claw deformity.
UNASSIGNED: A one-year-old girl child presented to the dermatology clinic with asymptomatic lesions since childhood with no improvement, with multi- hypopigmented skin lesions on the trunk and extremities since birth as linear erosions that heal gradually during few days, leaving peripheral hypopigmentation with hyperpigmentation with anomalies of limbs and nails and delayed development. She was born by normal vaginal delivery and weighed 2.5 kg at birth. None of the family members had such features. She had dental enamel anomaly and partial anodontia in the lower jaw. Sparse hair and partial alopecia (scalp, eyebrows and eyelashes) were recorded.
UNASSIGNED: Focal dermal hypoplasia is a congenital skin disease with a unique clinical feature. Thorough examination of the extremities is indicated for early proper genetic counseling and therapy.

Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants.
We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes.
Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.

Focal dermal hypoplasia (Goltz syndrome), is an exceedingly rare X-linked dominant genetic disorder. It is a multisystem disease, but it is hallmarked by characteristic skin changes. Focal dermal hypoplasia typically occurs in females (90%), and males are thought to only survive through having either a sporadic new mutation or somatic mosaicism. This report details a 48-year-old male diagnosed with predominately unilateral focal dermal hypoplasia that was reviewed decades post his initial diagnosis. He presented with multiple atrophic hyperpigmented macules and fat herniation along the lines of Blaschko, across primarily the right side of the body. Skin biopsy is the mainstay for the diagnosis and therefore dermatologists need to be aware of the classical cutaneous findings of familial dermal hypoplasia to ensure accurate diagnosis. Familial dermal hypoplasia is best managed through the collective minds of multidisciplinary teams.