Nevus Flammeus Research Articles

Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype

BackgroundBohring-Opitz syndrome (BOS) is a rare genetic disorder characterised by a recognisable craniofacial appearance and a typical ‘BOS’ posture. BOS is caused by sporadic mutations ofASXL1. However, several typical patients...

Phakomatosis pigmentovascularis: Birthmarks which might not be so benign

Introduction: Mongolian blue spot (Dermal melanocytosis) is a common birth mark. We describe the case of an infant with extensive cutaneous lesions who presented with apnoea. Case: This baby was born following an uncomplicated pregnancy to unrelated Asian parents in good condition. She had extensive vascular malformation and dermal melanosis on all limbs and abdomen. She had macroglossia and hemihypertrophy of left upper limb. A clinical diagnosis of Phakomatosis pigmentovascularis was made. At two months of age, she presented with apnoea needing intubation and ventilation. She was noted to have subglottic stenosis. Her tone was increased and she had hyperreflexia. Her intra ocular pressures were elevated. MRI of brain showed a global reduction in brain volume with extra axial dilatation of the ventricles. The left hemisphere was smaller and more atrophic. There were extensive abnormal tortuous veins over the surface of the entire brain and extensive ischaemia in both cerebral hemispheres. Following discussions with the family, she was extubated with a view for palliation. She passed away one week after discharge. Discussion: Phakomatosis pigmentovascularis (PPV) is a rare disorder characterised by combination of dermal melanocytic lesions and vascular malformations. It is classified based on cutaneous phenotypes. 50% of cases have systemic involvement involving the eye, brain, overgrowth of soft tissue and melanoma. PPV without systemic complications is benign and requires no treatment. Pathogenesis is not fully established. It has been proposed that it is associated with post zygotic mutations in genes encoding Gα subunits of heterotrimeric G proteins like GNAQ or GNA11. Early death and subglottic stenosis like our case has not been described. Genetic test result is awaited. Conclusion: Extensive or aberrant Mongolian blue spots present along with naevus flammeus should alert the clinician of the possibility of this rare condition with potentially significant systemic complications.

Pathophysiology, diagnosis, and management of glaucoma associated with Sturge-Weber syndrome.

Sturge-Weber syndrome (SWS), also known as encephalotrigeminal angiomatosis, is a condition which includes leptomeningeal hemangioma, facial angiomatosis or nevus flammeus, and ocular changes. SWS can lead to severe complications of anterior segment involving conjunctiva and eyelids, whereas posterior segment of the eye may also be affected by diffuse choroidal hemorrhages. This article was written with the objectives to determine the pathophysiology, diagnosis, and treatment of glaucoma associated with this rare and challenging disorder. A detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Forty-five articles matched our inclusion criteria that were included in this systematic review. Glaucoma is the one of the commonest ocular manifestations of SWS. It is caused by anterior chamber malformations, increased pressure in the episcleral veins, and changes in ocular hemodynamics. Glaucoma associated with SWS is usually congenital but can develop adults as well. The treatment of glaucoma associated with SWS is quite challenging because of early-onset, severe visual field impairment at the time of diagnosis, and unresponsiveness to standard medical treatment. Several surgical procedures have been devised but the long-term control of the intraocular pressure and visual function remain unsatisfactory. Modifications in the filtration surgery techniques and use of newer anti-fibrotic agents have produced good control of intraocular pressure. Management of glaucoma associated with SWS is multi-dimensional and needs both medical and surgical interventions for better control. The treatment should be devised on case to case basis depending upon the intraocular pressure, stage of the disease, and type of glaucoma.

A Final Diagnosis of Port Wine Stain or Nevus Flammeus

Clinical Image: A 27 year old female patient reported to the department of oral medicine and radiology with a chief complains of deposits on teeth. Past medical and dental history was non-contributory. Extra oral examination revealed a well demarcated purplish red discoloration seen on left side of the face extending anteriorly from supra-orbital margin involving the upper eyelid, on asking the occurrence of the patient gave history of occurrence since birth. Intraoral findings revealed no significant correlation with the discoloration. A final diagnosis of Port wine stain or Nevus flammeus was considered for this atypical type of pigmentation.

Beckwith-Wiedemann Syndrome Review: A Guide for the Neonatal Nurse.

Beckwith-Wiedemann syndrome (BWS) is the most common pediatric overgrowth syndrome. Features characteristic of the BWS phenotype include both physical attributes, such as macroglossia, abdominal wall defects, gigantism, nevus flammeus, visceromegaly, and mid-face hypoplasia, as well as biochemical abnormalities such as hypoglycemia. It is essential for the neonatal nurse to be able to recognize BWS in the patient's early years of life because of the increased frequency of medical complications, malformations, and the increased risk of embryonic malignancies. This article focuses on the presentation of BWS as an aid to early detection.

Phacomatosis Cesioflammea with Cutis Marmorata-like Lesions and Unusual Extracutaneous Abnormalities: Is It a Distinct disorder?

A 2-month-old boy was presented with widespread lateralized blue macules (nevus cesius), an extensive nevus flammeus, and large patches of cutis marmorata telangiectatica congenita. Moreover, he had macrocephaly, a coarse facial appearance with depressed nasal bridge, retinal abnormalities, septal defects of the heart, and obliteration of the left brachiocephalic vein and major veins of the left arm with pronounced collateralization. The multisystem disorder of this boy cannot be categorized within the present classification of distinct types of phacomatosis pigmentovascularis. Although some similar complex cases have previously been reported, it seems too early to give them a specific name. Rather, the present case should be included, so far, into the group of unclassifiable types of phacomatosis pigmentovascularis.

Beckwith Wiedemann Syndrome: A Case Report

The baby with Beckwith Wiedemann Syndrome (BWS) usualy presents with exomphalos, macroglossia and gigantism. In addition, some children with BWS have other findings including: nevus flammeus, prominent occiput, midface hypoplasia, hemihypertrophy, genitourinary anomalies (enlarged kidneys), cardiac anomalies, musculoskeletal abnormalities, and hearing loss. Incidence of one in 13,700 live birth. As children with BWS are at increased risk of childhood cancer, they should follow up strictly for cancer screening. We are reporting this type of a case who has got Exomphalos, Macroglossia, Gigantism and Hemihypertrophy. We have corrected the exomphalos and advised him for follow up for cancer screening.Faridpur Med. Coll. J. Jul 2015;10(2): 87-88

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes.

Sturge Weber Syndrome

Sturge weber syndrome is a rare sporadic condition of mesodermal phacomatosis, also called encephalotrigeminal angio­matosis (synonyms : fourth phacomatosis or mother spot), is a neurocutaneous disorder with angiomas that involve the leptomeninges (leptomeningeal angiomas) and the skin of the face (purple colored flat cutaneous haemangiomas ), typically in the ophthalmic (V1) and maxillary (V2) distributions of the trigeminal nerve. The hallmark of sturge weber syndrome is a facial cutaneous venous dilation, also referred to as a nevus flammeus or port wine stain (PWS). Because of the rarity, we report here a one & half year old male child who presented with features of the Sturge Weber Syndrome on both side of face.

Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder predisposing to tumorigenesis that results from abnormal expression or function of imprinted genes of chromosome 11p15.5. Forty-seven patients in Taiwan with clinical suspicion of BWS were referred for diagnostic testing based on methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-resolution quantitative methylation profiling. Twenty-eight patients received a clinical diagnosis of BWS (the presence of 3 major features or 2 major features and at least 1 minor feature), 18 had suspected BWS (the presence of at least 1 major feature), and 1 had isolated Wilms' tumor. Nineteen patients were identified with IC2 hypomethylation (including 1 with isolated Wilms' tumor), 1 with IC1 hypermethylation, 2 with paternal uniparental disomy, and 1 with CDKN1C mutation. Several clinical features were found to be statistically different (P<0.05) between the 2 groups-clinical diagnosis of BWS (n=28) or suspected BWS (n=18)-including macroglossia, pre- or postnatal gigantism, abdominal wall defect, ear creases, facial nevus flammeus, BWS score, and the molecular diagnosis rate. Molecular lesion was detected in 81% of patients with the presence of three major features, compared with 33% and 28% of those with two or one major feature, respectively. The mean BWS score was 5.6 for 19 subjects with "IC2 hypomethylation", compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1 hypermethylation was 6 and 7, respectively. The BWS score was positively correlated with the molecular diagnosis rate (P<0.01). The BWS database of epigenotype, genotype, and phenotype is expected to promote better genetic counseling and medical care of these patients.

PHACOMATOSIS PIGMENTOVASCULARIS TYPE IIA – A CASE REPORT

Phacomatosis pigmentovascularis (PPV) is a rare syndrome characterized by capillary vascular malformation and pigmentary nevus but with a wide variability in clinical presentation. A case of a 9-month-old patient is reported, who presented with capillary malformation and hemihypertrophy. These features typically are seen in Klippel–Trenaunay (KT) syndrome, a syndromic type of congenital vascular malformation. However, in addition, this child had large persistent Mongolian spots, the presence of which allowed us to classify this case as PPV, type II. This is a condition with a clinical course not always benign as KT syndrome. Key words: Mongolian spots, Nevus flammeus, Vascular malformations

Presence of Autoimmune Diseases in Alopecia Areata Patients and Their Families and Its Effect on Prognosis

Objective: We aimed to investigate the role of autoimmunity in the etiopathogenesis of alopecia areata (AA) and the effects of the coexisting autoimmune diseases on the prognosis of AA. Methods: The records of 134 AA patients diagnosed in the dermatology and venereology outpatient clinic were retrospectively analyzed for the history of concomitant autoimmune disease and the family history for autoimmune diseases. Results: Of the 134 patients, 79 were males, 55 were females. The rate of autoimmune disease was 16.4%. The rate of autoimmune disease was found significantly higher in the females (p=0.034) and in the patients with a positive family history of autoimmune disease (p=0.011). No significant relationship was found between the coexistence of an autoimmune disease and the duration, type, severity of the disease, age at disease onset, nail involvement, atopy, nevus flammeus and family history of AA. The rate of the family history of autoimmune disease within the AA patients was 16.4%. Conclusion: The high rate of autoimmune disease in AA, prominent high rate of autoimmune disease in females, high rate of family history of autoimmune disease might prove the role of the autoimmunity in the etiopathogenesis of AA and suggested AA as an autoimmune disease. The coexistence of the autoimmune disease in AA has no relationship with poor prognosis.

Term Newborn with Unilateral Craniofacial Defects

A newborn presents with congenital right-sided craniofacial asymmetry, absence of right eye and ear, and small facial structures on the right (Fig 1). Figure 1A and B: Front and profile views of craniofacial defects, including absence of right orbit, right microtia, depressed right fronto-parietal area and facial asymmetry. ### Prenatal and Birth Histories ### Presentation The infant was transferred to the neonatal intensive care unit from an outside hospital with multiple craniofacial anomalies. His admission physical examination was notable for a depression on the right side of the skull and face with a depressed right frontoparietal bone, absence of right eye, right microtia, and a nevus flammeus noted over the glabella and nose. ### Vital Signs ### Physical Examination

Nevus Flammeus: A Rare Case Report

Port-wine stain (PWS), also referred to as “nevus flammeus,” is a vascular malformation of skin which appears as red to violaceous patches on the surface of the skin. There is no hereditary predilection and no known risk factors. Rarely, may it, also, be acquired secondary to trauma. It comes under a group of disorders known as vascular malformations and may be seen as a part of syndromes like Sturge-Weber syndrome, a rare neuro-cutaneous disorder, sporadic in occurrence, without any identified underlying genetic abnormality. It is also termed as encephalo-trigeminal angiomatosis, manifesting clinically, as a cutaneous lesion, a nevus flammeus that involves the region innervated by the branches of the trigeminal nerve. Herewith, we are reporting a case with facial port wine stains with enlargement of middle third of face, upper lip and gingival tissues on right side as described.

Alopesi Areatalı Hastaların Klinik ve Sosyodemografik Özellikleri ve Bu Özellikler Arası İlişkiler

Objective: Alopecia areata (AA) is a chronic inflammatory disease that affects hair follicles. This study aimed to determine the clinical and sociodemographic characteristics of patients with AA, and the correlations between them. Material and Methods: A hundred and fifty three AA patients (49 female and 104 male with a mean age 28 years) were included in the study. Their sociodemographic characteristics, clinical data and etiologic data were recorded. The severity of disease was determined using Severity of Alopecia Tool (SALT) scores. Results: Mean SALT scores increased significantly in patients whose onset of the disease was in the childhood, and in patients who had multiple episodes of AA previously. Mean SALT scores also increased for patients with a positive family history of AA, nail involvement, ophiasis, nevus flammeus or autoimmune diseases (p< 0.05). No significant difference was found between SALT scores, and sex and presence of atopy. Conclusion: Early stages of the disease, positive family history of AA, the presence of the nail involvement, nevus flammeus, ophiasis, and autoimmune diseases were associated with severe involvement in this study. Considering the correlation between these factors in patient management is thought to be helpful in selecting a more appropriate and effective treatment.

Oral and extraoral manifestationse of sturge-Weber syndrome: A rare finding

Sturge-Weber syndrome (SWS) is a rare congenital developmental disorder characterized by unilateral cutaneous vascular malformation (nevus flammeus or port-wine stains) in association with ipsilateral leptomeningeal angiomatosis and glaucoma. This article presents a case of SWS associated with gingival hyperplasia and pyogenic granuloma.

A Case of Wyburn-Mason Syndrome with Facial Nevus Flammeus and the Associated Optical Coherence Tomography Findings

Purpose: To describe a case of Wyburn-Mason Syndrome, which is a rare phakomatosis, and its associated optical coherence tomography findings. Case summary: A 5-year-old boy was referred to our clinic for decreased vision in his right eye. He had nevus flammeus on his right forehead, upper eyelid, and cheek. His best corrected visual acuity was hand motion in the right eye, in which a relative afferent pupillary defect was noted. Fundus examination of the right eye showed marked dilation and tortuosity of retinal vessels, which could not be discriminated between arteries and veins on the posterior pole. Optical coherence tomography showed multiple large intraretinal vessels without involvement of the internal limiting membrane. Cerebral angiography revealed arteriovenous malformations (AVMs) and feeder vessels from the internal carotid artery to the ophthalmic artery, extending to the ethmoidal artery in the nasal cavity. Conclusions: Wyburn-Mason syndrome is a rare phakomatoses and shows unique retinal AVM. Misdiagnosis or undertreatment of Wyburn-Mason syndrome can lead to serious complications. Patients with facial nevus flammeus should undergo thorough ocular examinations to rule out this disorder. Optical coherence tomography is a useful method for understanding structural features of retinal vascular malformations in Wyburn-Mason syndrome. J Korean Ophthalmol Soc 2016;57(8):1333-1338

Phacomatosis cesioflammea in a 5-week-old infant

A 5-week-old male infant presented with extensive lesions of nevus flammeus and Mongolian spots affecting the face, trunk, buttocks and extremities. In addition, the child had ocular melanosis and a cafe-au-lait spot on the trunk. The case is being reported on account of its rarity.

Severe Rhabdomyolysis in Phacomatosis Pigmentovascularis Type IIb associated with Sturge-Weber Syndrome

Phacomatosis pigmentovascularis (PPV) is a rare syndrome characterized by concurrent nevus flammeus (capillary malformation) and pigmentary nevus. According to current research, the major pathophysiologic mechanism in PPV is venous dysplasia with resultant compensatory collateral channels and venous hypertension. Arterial involvement is rare. We herein report our experience on renovascular hypertension, intermittent claudication, and severe rhabdomyolysis due to diffuse stenosis of multiple arteries in a patient with PPV type IIb associated with SWS.

“Gestalt diagnosis” for children with suspected genetic syndromes

Gestalt identification is the process by which healthcare practitioners actively organize clinical perceptions into specific diagnostic ideas. This implies that clinicians, in particular geneticists, have the ability to quickly generate diagnostic hypotheses in absence of complete information, simply on the basis of combination of specific facial dysmorphisms or particular elements of the clinical history. This is particularly frequent in clinical genetics because the “facial dysmorphisms” of the patient represent often the most specific clinical criteria of the syndrome itself. Down [1], Cornelia de Lange [2], Wolf-Hirshhorn [3], Noonan [4], Rubistein-Taybi [5] Kabuki [6], Treacher Collins [7] and Williams syndrome [8] are examples well known to pediatricians but this is true for the great majority of genetic syndromes. In these situations facial dysmrphisms can have variable expression between different patients (also in the same family) or can become more or less evident over time. Moreover the “gestalt process” can also be applied in case of specific auxologic and/or neurologic evolution. In patients with Prader-Willi syndrome (PWS) in the first months of life hypotonia is evident and tends to improve between 8 and 11 months of age; poor growth and feeding problems are frequent too. Later on hypotonia improves and feeding difficulties are replaced by hyperphagia and obesity. This typical evolution can permit to suspect in every phase PWS diagnosis and to perform methylation test for 15q11.2 region [9]. Some neuro pediatricians suggest that Angelman syndrome's EEG pattern is typical enough to be recognized by sensitized professionals [10]. A specific behavioral phenotype, including significant sleep disturbance, stereotypies and oppositional behavior, is pretty characteristic of Smith-Magenis syndrome [11]. Again, PTEN gene testing may be considered for patients with extreme macrocephaly associated with intellectual disability/autistic behaviour [12]. Within overgrowth syndrome, Beckwith-Wiedemann syndrome (BWS) can be easily recognized thanks to the association between hemi-hypertrophy, macroglossia, abdominal wall defects and frontal nevus flammeus [13]. Finally within patients with short stature the evidence of disproportion between crown-rump and overall lengths, or between limbs and trunk univocally direct the diagnosis toward the skeletal dysplasias [14]. In conclusion the knowledge of facial features and/or natural history (auxological, neurological behavioural etc) of the most common genetic syndromes can help pediatricians in hypothesizing them through a “gestalt process” in order to quickly confirm the clinical diagnosis with the specific genetic tests.