Clinical and molecular evaluation of 13 Brazilian patients with Gomez-López-Hernández syndrome.

We aim to characterize patients with Gomez-López-Hernández syndrome (GLHS) clinically and to investigate them molecularly. A clinical protocol, including a morphological and neuropsychological assessment, was applied to 13 patients with GLHS. Single-nucleotide polymorphism (SNP) array and whole-exome sequencing were undertaken; magnetic resonance imaging was performed in 12 patients, including high-resolution, heavily T2-weighted sequences (HRT2) in 6 patients to analyze the trigeminal nerves. All patients presented alopecia; two did not present rhombencephalosynapsis (RES); trigeminal anesthesia was present in 5 of the 11 patients (45.4%); brachycephaly/brachyturricephaly and mid-face retrusion were found in 84.6 and 92.3% of the patients, respectively. One patient had intellectual disability. HRT2 sequences showed trigeminal nerve hypoplasia in four of the six patients; all four had clinical signs of trigeminal anesthesia. No common candidate gene was found to explain GLHS phenotype. RES does not seem to be an obligatory finding in respect of GLHS diagnosis. We propose that a diagnosis of GLHS should be considered in patients with at least two of the following criteria: focal non-scarring alopecia, rhombencephalosynapsis, craniofacial anomalies (brachyturrycephaly, brachycephaly or mid-face retrusion), trigeminal anesthesia or anatomic abnormalities of the trigeminal nerve. Studies focusing on germline whole genome sequencing or DNA and/or RNA sequencing of the alopecia tissue may be the next step for the better understanding of GLHS etiology.

Gomez-López-Hernández syndrome: A case report with clinical and molecular evaluation and literature review.

Gomez-López-Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES-associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.

Expansion of the phenotypic spectrum and description of molecular findings in a cohort of patients with oculocutaneous mosaic RASopathies.

BACKGROUND: Postzygotic KRAS, HRAS, NRAS, and FGFR1 mutations result in a group of mosaic RASopathies characterized by related developmental anomalies in eye, skin, heart, and brain. These oculocutaneous disorders include oculoectodermal syndrome (OES) encephalo-cranio-cutaneous lipomatosis (ECCL), and Schimmelpenning-Feuerstein-Mims syndrome (SFMS). Here, we report the results of the clinical and molecular characterization of a novel cohort of patients with oculocutaneous mosaic RASopathies. METHODS: Two OES, two ECCL, and two SFMS patients were ascertained in the study. In addition, two subjects with unilateral isolated epibulbar dermoids were also enrolled. Molecular analysis included PCR amplification and Sanger sequencing of KRAS, HRAS, NRAS, and FGFR1 genes in DNA obtained from biopsies (skin/epibulbar dermoids), buccal mucosa, and blood leukocytes. Massive parallel sequencing was employed in two cases with low-level mosaicism. RESULTS: In DNA from biopsies, mosaicism for pathogenic variants, including KRAS p.Ala146Thr in two OES subjects, FGFR1 p.Asn546Lys and KRAS p.Ala146Val in ECCL patients, and KRAS p.Gly12Asp in both SFMS patients, was demonstrated. No mutations were shown in DNA from conjunctival lesions in two subjects with isolated epibubar dermoids. CONCLUSION: Our study allowed the expansion of the clinical spectrum of mosaic RASopathies and supports that mosaicism for recurrent mutations in KRAS and FGFR1 is a commonly involved mechanism in these rare oculocutaneous anomalies.

Phacomatosis pigmentovascularis of cesioflammea type

Abstract Phacomatosis pigmentovascularis is a rare syndrome, defined as the simultaneous presence of vascular nevus and melanocytic nevus in the same patient. We report the case of a 53-year-old woman presented with dermal melanosis and extensive vascular nevus, which match the typical manifestations of phakomatosis pigmetovascularis of cesioflammea type, according to Happle's classification. The rare occurrence of this genodermatosis and the clinical exuberance of the skin lesions motivated this case report.

5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

Phacomatosis pigmentovascularis of cesioflammea type.

Phacomatosis pigmentovascularis is a rare syndrome, defined as the simultaneous presence of vascular nevus and melanocytic nevus in the same patient. We report the case of a 53-year-old woman presented with dermal melanosis and extensive vascular nevus, which match the typical manifestations of phakomatosis pigmetovascularis of cesioflammea type, according to Happle's classification. The rare occurrence of this genodermatosis and the clinical exuberance of the skin lesions motivated this case report.

The case of a boy with nevus of Ota, extensive Mongolian spot, nevus flammeus, nevus anemicus and cutis marmorata telangiectatica congenita: a unique instance of phacomatosis pigmentovascularis.

Phacomatosis pigmentovascularis is a rare, congenital condition characterized by a combination of cutaneous melanocytic lesions and vascular malformation. We discuss an entirely unique case of Phacomatosis pigmentovascularis with nevus of Ota, extensive Mongolian spot, nevus flammeus, nevus anemicus and cutis marmorata telangiectatica congenita, which may represent a heretofore undescribed variant of phacomatosis pigmentovascularis.

The case of a boy with nevus of Ota, extensive Mongolian spot, nevus flammeus, nevus anemicus and cutis marmorata telangiectatica congenita: a unique instance of phacomatosis pigmentovascularis

Phacomatosis pigmentovascularis is a rare, congenital condition characterized by a combination of cutaneous melanocytic lesions and vascular malformation. We discuss an entirely unique case of Phacomatosis pigmentovascularis with nevus of Ota, extensive Mongolian spot, nevus flammeus, nevus anemicus and cutis marmorata telangiectatica congenita, which may represent a heretofore undescribed variant of phacomatosis pigmentovascularis.

Gómez-López-Hernández syndrome in a child born to consanguineous parents: new evidence for an autosomal-recessive pattern of inheritance?

BACKGROUND: Gómez-López-Hernández syndrome is a rare genetic disease characterized by scalp alopecia with trigeminal anesthesia, brachycephaly or turribrachycephaly, midface retrusion, and rhombencephalosynapsis. We report the second case with this condition who presented with consanguineous parents. PATIENT: This boy was evaluated shortly after birth because of suspected craniosynostosis. He was the only son of healthy, consanguineous parents (his maternal grandmother and his paternal great-grandfather were siblings). His examination was notable for turribrachycephaly, prominent forehead, bilateral parietotemporal alopecia, midfacial retrusion, anteverted nostrils, micrognathia, low-set and posteriorly rotated ears, and short neck with redundant skin. Radiographs and tridimensional computed tomography scan of skull revealed lambdoid craniosynostosis. Brain magnetic resonance imaging revealed complete rhombencephalosynapsis, aqueductal stenosis, fused colliculi, abnormal superior cerebellar penducle, mild ventriculomegaly, and dysgenesis of the corpus callosum. CONCLUSIONS: Since its first description, 34 patients with this condition have been reported. The etiology of Gómez-López-Hernández syndrome is unknown. However, it is noteworthy that the patient in this report presented with a family history of consanguinity because this finding reinforces the possibility of an autosomal-recessive inheritance for this condition.

Phacomatosis pigmentovascularis type IIa--case report.

Phacomatosis Pigmentovascularis is a rare syndrome characterized by capillary malformation and pigmentary nevus. A case of a 2-year-old patient is reported, who presented extensive nevus flammeus and an aberrant Mongolian spot, without systemic disease, manifestations that allow us to classify this case as type IIa Phacomatosis Pigmentovascularis, according to Hasegawa's classification.

Phacomatosis pigmentovascularis type IIa - case report / Facomatose pigmentovascular tipo IIa - relato de caso

Phacomatosis Pigmentovascularis is a rare syndrome characterized by capillary malformation and pigmentary nevus. A case of a 2-year-old patient is reported, who presented extensive nevus flammeus and an aberrant Mongolian spot, without systemic disease, manifestations that allow us to classify this case as type IIa Phacomatosis Pigmentovascularis, according to Hasegawa's classification.

A Facomatose Pigmentovascular, síndrome rara, é caracterizada pela presença concomitante de malformação capilar e nevos pigmentares. Relata-se o caso de um paciente de dois anos de idade com malformação capilar extensa e mancha mongólica aberrante sem comprometimento sistêmico, manifestações que o incluem no tipo IIa na classificação da Facomatose Pigmentovascular, segundo Hasegawa.

Are patients with encephalocraniocutaneous lipomatosis at increased risk of developing low-grade gliomas?

INTRODUCTION: Cancer-prone genetic disorders are responsible for brain tumors in a considerable proportion of children. Additionally, rare genetic syndromes associated to cancer development may potentially disclose genetic mechanisms related to oncogenesis. METHOD: We describe two pediatric patients with encephalocraniocutaneous lipomatosis (ECCL), a very rare genetic syndrome with around 60 reported cases, which developed low-grade astrocytoma at 3 and 12 years of age. RESULTS: Patients with ECCL seem to be at risk of benign forms of osseous tumors such as ossifying fibromas, odontomas, and osteomas. CONCLUSION: The association between brain tumor and ECCL was previously reported only once, in a pediatric case of a mixed neuronal-glial histology. Whether ECCL may be a genetic condition of predisposing brain tumor in children strongly needs to be addressed.

Melanosis neurocutánea: Comunicación de un caso y revisión de la bibliografía / Neurocutaneous melanosis: Case report and literature review

La melanosis neurocutánea se caracteriza por la proliferación de melanocitos y depósitos de melanina en el sistema nervioso central asociada con nevos melanocíticos gigantes. Los pacientes con nevos melanocíticos congénitos gigantes localizados en el eje axial posterior (dorso, nuca o cabeza) o múltiples nevos melanocíticos congénitos pequeños son los que tienen mayor riesgo de presentarla. En la mayoría de los pacientes la melanosis neurocutánea es asintomática y se detecta como un hallazgo en los estudios por imágenes; sin embargo, los casos que desarrollan síntomas tienen mal pronóstico y el óbito se produce antes de los 3 años de iniciados. Se presenta una paciente con un nevo melanocítico congénito gigante y múltiples satelitosis, con compromiso asintomático del sistema nervioso central. Se destaca la importancia del seguimiento multidisciplinario de estos niños con el fn de detectar, en forma precoz, cualquier signo o síntoma neurológico que pudiesen desarrollar, como así también la presencia de melanoma.

Neurocutaneous melanosis is characterized by an increased number of melanocytes and melanin deposit in central nervous system associated with giant melanocytic congenital nevi. Patients with multiple satellite nevi or giant cutaneous melanocytic nevus in a midline location (overlying the back, neck or head) have more likelihood of having neurocutaneous melanosis. In most patients, the neurocutaneous melanosis is asymptomatic, only detectable by MRI; nevertheless, those patients with clinical manifestations have a poor prognosis, dying within 3 years of initial neurological manifestations. We present a patient with giant melanocytic congenital nevi and multiple satellite nevi associated with asymptomatic neurocutaneous melanosis. We emphazise the importance of multidisciplinary evaluation in order to detect early neurological symptoms and/or melanoma.