A de novo truncating mutation in ASXL1 associated with segmental overgrowth

Mutations in genes involved in chromatin remodelling have been implicated in broad phenotypes of congenital abnormalities and neurodevelopment. However, limited genotype–phenotype correlations are available for some of the rarestgenetic disorders that affect chromatin regulation. We hereby describe a 12-year-old girl presented at birth with severe hypotonia, developmental delay, a mid-line capillary malformation and distinctive craniofacial features. During the natural history of her disease, the girl developed severe spasticity and drug-resistant seizures, leading to a diagnosis of Bohring–Opitz syndrome (BOS). We performed whole-exome sequencing (WES) and identified a de novo mutation in ASXL1 (c.2033dupG) which results in the introduction of a premature stop codon (p.R678fs*6). ASXL1 encodes a polycomb repressive complex protein implicated in chromatin regulation and de novo mutations are a known cause of BOS. Phenotypes with segmental craniofacial overgrowth associated to midline capillary malformations enlarge the clinical spectrum of BOS at onset and further expand the differential diagnosis in ASXL1 mutation carriers.

Clinical Presentation and the Treatment of Glaucoma in Patients with a Facial Port-wine Stain

PURPOSE: To characterize the development of glaucoma, age of glaucoma onset, and treatments for patients with a facial port-wine stain (PWS). METHODS: We performed a retrospective analysis of the medical records of 58 patients (116 eyes) with facial PWS between January 2000 and August 2016. We noted patients' age at the initial examination, cup-to-disc ratio, corneal diameter, occurrence of ocular hypertension, development of glaucoma, age of glaucoma onset, and treatments. We compared the clinical features of eyes that developed glaucoma with those that did not develop glaucoma. Among those eyes with glaucoma, we investigated the differences between eyes that underwent surgery and those that did not undergo surgery. RESULTS: Among the 58 patients with a facial PWS (116 eyes), glaucoma was diagnosed in 38 patients (46 eyes; 39.66%). Of these, 26 patients (27 eyes; 58.69%) underwent glaucoma surgery. PWS-associated glaucoma usually developed by the age of 2 years (85.61%). In all patients, glaucoma developed on the same side of the face as the PWS. Of the 58 patients, 19 (32.76%) showed neurological symptoms, including seizures, developmental delays, intellectual disabilities, or hemiplegia, and 32 (55.17%) were diagnosed with Sturge-Weber syndrome. The mean number of glaucoma surgeries was 1.55 ± 0.93. The initial surgery included trabeculectomy (7 eyes), trabeculotomy (5 eyes), combined trabeculotomy/trabeculectomy (13 eyes), and aqueous drainage device insertion (2 eyes). The mean age at the first surgery was 35.14 ± 50.91 months. In 18 of 27 eyes (66.67%), the postoperative intraocular pressure (IOP) was controlled to below 21 mmHg, but 9 eyes (33.33%) showed elevated IOP and required a reoperation. CONCLUSIONS: PWS can be accompanied by ocular hypertension or glaucoma, so patients require regular ophthalmic examinations. When glaucoma occurs, it often does not respond to medication, making it difficult in some cases to control the IOP, so appropriate glaucoma surgery is necessary.

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.

A Tethered Cord with Hemivertebra: A Case Report and Review of Literature

Spinal dysraphisms are defined as open and closed dysraphisms. A hemivertebra is a congenital condition seen in 61% of patients with congenital anomalies. The first report of the excision of a hemivertebra was by Royle in 1928. A sixteen-year-old girl was admitted to our clinic with a congenital stain on the waist and a normal neurological examination. No new cases have been reported in recent literature. Our case, which is also rare, is associated with a tethered cord only and no other congenital abnormalities.

Presentación atípica de morfea tipo malformación vascular símil con síndrome Parry-Romberg secundario / Atypical presentation of vascular malformation morphea simile Parry-Romberg syndrome secondary

La Morfea es una forma de presentación clínica de la esclerodermia localizada, que generalmente se manifiesta como una placa eritematosa con un anillo lila que evoluciona a placa atrófica. Existen presentaciones atípicas de morfea en que al inicio la piel afectada simula ser una malformación vascular tipo nevus flameus o mancha en vino de oporto. El Síndrome Parry-Romberg corresponde a una morfea localizada que se caracteriza por hemiatrofia facial que afecta la funcionalidad de la cara y que puede comprometer piel, tejido muscular y hueso. El objetivo de este artículo es presentar, por medio de un caso clínico, una entidad rara de morfea que al inicio simula ser un nevusflameus. El nevus flameus adquirido es raro y requiere tiempo para que se inicien los cambios escleróticos. Se presenta el caso de un niño de 8 años que consultó por un cuadro atípico sospechoso de nevus flameus y que al cabo de 3 años evolucionó como una hemiatrofia facial progresiva. Los pacientes con diagnóstico de nevus flameus adquirido deberían monitorizarse en busca de signos de evolución a morfea y si la ubicación es en la cara siempre debe sospecharse un Síndrome Parry-Romberg para el inicio temprano de terapia y disminuir las consecuencias asociadas.

Morphea is a clinical presentation of the localized scleroderma, which usually manifests as an erythematous plaque with a purple halo that evolves to an atrophic plaque. There are atypical presentations of the morphea that, at the beginning, the affected skin simulates being a vascular malformation port wine stain simil. The Parry-Romberg Syndrome corresponds to a localized morphea that characterizes for showing a facial hemiatrophy that affects the facial functionality and may compromise the skin, muscular tissue and bones. The objective of this paper is to present, through a clinical case, a rare entity of the morphea that at the beginning simulates being a port wine stain. The acquired port wine stain is rare and requires some time to show sclerotic changes. A clinical case of an 8 years old patient that consulted for a suspicion of an atypical clinical picture of port wine stain and that after 3 years evolved in a progressive facial hemiatrophy is presented. The patients with an acquired port wine stain diagnosis should be monitored to find signs of an evolution to morphea and if it is located on the face there should always be a suspicion of a Parry Romberg syndrome in order to start earlier the therapy and reduce the associated consequences.

Prominent Orofacial Findings In Klippel - Trenaunay Syndrome.

Klippel-Trenaunay syndrome is a triad of congenital anomalies characterized by nevus flammeus, varicosities, and unilateral bony and soft tissue hypertrophy. Orofacial manifestations include facial asymmetry, jaw enlargement, and malocclusions as well as premature tooth eruption. Presented here is an illustrative report of Klippel Trenaunay syndrome in a 30 year old male patient showing all the characteristic findings.

A Case of Klippel-Trenaunay-Weber Syndrome with Facial Hemihypertrophy and Hemimegalencephaly / 대한소아신경학회지

Klippel-Trenaunay-Weber syndrome(KTWS) is a rare, and sporadically occurring disorder characterized by hemihypertrophy(unilateral limb hypertrophy), varicose veins, hemangiomas and occasionally arteriovenous malformations. In 1900, noted French physicians Klippel and Trenaunay first described the syndrome in 2 patients presenting with port-wine stains and varicosities of extremities associated with hypertrophy of the affected limb's bones and soft tissues. There are other, and less frequent abnormalities. These may include limbs that are atrophic, fingers and toes that are disproportionately large or small, digits that are webbed(syndactyly), and too many digits(polydactyly), or too few digits(oligodactyly). The hemangiomas can occur in internal organs including the intestinal and the urinary tract systems. The exact cause of KTWS remains to be elucidated, although several theories exist. Most cases are sporadic, although a few cases in the literature report a multifactorial patterns of inheritance. We report a case of Klippel-Trenaunay-Weber syndrome in a 3-year-old boy who had hypertrophy of the left facial bones and tissues, large hemangiomas on the right trunk and back, and hypertrophy of the right upper and lower limb's soft tissues.

A Case of Tufted Angioma Arising within a Nevus Flammeus / 대한피부과학회지

Tufted angioma is an uncommon, slowly-progressive vascular tumor, found typically in infants, young children and sometimes at birth or during adulthood. It shows a characteristic histopathologic finding, the so-called "cannonball" appearance. Various tumors can be developed in the nevus flammeus, such as pyogenic granuloma, basal cell carcinoma, squamous cell carcinoma, giant proliferative hemangioma and lymphangioma circumscriptum. Tufted angioma can be also accompanied with nevus flammeus and the coexistence of tufted angioma and nevus flammeus is a very rare condition. We report a case of tufted angioma arising within nevus flammeus in the left axilla of a 47 year-old female.

A Case of Angioma Serpiginosum Accompanied with Ipsilateral Nevus Flammeus on the Hand / 대한피부과학회지

Angioma serpiginosum is an acquired benign vascular neoplasm characterized by minute purple-colored, grouped nonpalpable punta on the extremities. However, nevus flammeus is a congenital vascular malformation that shows unilateral red macules. Although the evidence for association between vascular tumor and malformation have been posed, angioma serpiginosum is known to be rarely associated with nevus flammeus. We herein report a rare case of angioma serpiginosum accompanied with nevus flammeus on the ipsilateral hand.

Epithelioid Hemangioma Associated with Nevus Flammeus / 대한피부과학회지

Epithelioid hemangioma, the term which was first used by Enzinger and Weiss, is synonymous with angiolymphoid hyperplasia with eosinophilia. It defines a lesion occurring usually in the dermal and subcutaneous tissue of the head and neck, characterized by localized, marginated and relatively symmetrical proliferation of the capillaries around a medium-sized vessel with an epithelioid hyperplasia of endothelial cell. There is a marked inflammatory reaction composed of lymphocytes and eosinophils. We report a case of epithelioid hemangioma associated with nevus flammeus in a 53-year-old male. Histology revealed typical feature of epithelioid hemangioma that proliferation of dilated vessels with prominent endothelial cells surrounded by dense lymphoid cell infiltrates but no eosinophils were identified.

The Study on the Safety of General Anesthesia on Laser Treatment in Children / 대한피부과학회지

BACKGROUND: The earlier laser treatment of patients with nevus flammeus or Ota nevus prevent psychologic dysfunction due to unwanted cutaneous lesion and the increasing size of lesion. OBJECTIVE: Our purpose was to assess the safety and side effect of general anesthesia in the laser treatment of nevus flammeus or Ota nevus in children. METHODS: 25 children treated with laser for nevus flammeus or Ota nevus and underwent general anesthetic modality were included in this study. The age of patients, the size and the location of cutaneous lesions were noted. Most of children, after induction of anesthesia with thiopental and succinycholine, were maintained airway with intratracheal intubation. Some of children was done with intravenous anesthesia, propofol or ketamine. The results of laser treatment were assessed by photograph and clinical observation, based on a scale: excellent for 75-100% improvement, good for 50-75% improvement, fair for 25-50% improvement, poor for 0-25% improvement. RESULTS: 25 children treated with laser for nevus flammeus or Ota nevus were below 10 years old, eight of them were below 3 years old. The laser treatment was more effective in proportion with the number of laser treatment. After general anesthesia, all patients with laser treatment didn't appear the side effect of laryngeal spasm or apnea etc. Our data showed minimal risk and sequale of general anesthesia in the treatment of nevus flammeus or Ota nevus in children. CONCLUSION: The use of general anesthesia in the treatment of nevus flammeus or Ota nevus in children does not appear to be accompanied by increased risk.

A Study on the 216 Cases of Vascular Skin Lesion Treated by 585nm Flashlamp-Pumped Pulsed Dye Laser / 대한피부과학회지

BACKGROUND: 585nm flashlamp-pumped pulsed dye laser(FPDL) is a very effective treatment modality for vascular skin lesions with minimal risk of scarring by selective photothermolysis. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of FPDL in treating various vascular lesions in Korean patients, and in order to be helpful in expecting the treatment outcome and selecting the patients. METHODS: 216 cases treated with FPDL because of vasular skin lesions- nevus flammeus, telangiectasia, hemangioma and others- were included in this study. The results of the treatment were evaluated in the point of site, color, size, surface contour of lesions and patient's age in each condition. Photographs were obtained at baseline and 4~8 week intervals postoperatively. The results were assessed by two blinded assessors and surgeon after laser surgery, based on a scale of: poor for 0~25% improvement; fair for 25~50% improvement; good for 50~75% improvement; and excellent for 75~100% improvement. RESULTS: The commonest disease for treatment was nevus flammeus, followed by telangiectasia and strawberry hemangioma. In nevus flammeus, the lesions at upper eyelids, lower eyelids, upper lip skin and lesions which were darker in color and more elevated, responded less favorably. Age and sex of patients didn't affect the outcome. In telangiectasia, the results of treatment were above good in 83% of cases. In strawberry hemangioma, the results of treatment were above good in 73% of cases. CONCLUSION: FPDL is very effective in various vascular lesions, but one must keep in mind the differences in treatment outcome according to sites, color, size, surface contour of lesions.

Reflectance Spectrophotometry for the Evaluation of Therapeutic Effect of Falshlamp - pumped Pulsed Dye Laser for Nevus Flammeus / 대한피부과학회지

BACKGROUND: At present, flashlamp-pumped pulsed dye lasers are treatment of choice for the treatment of congenital capillary malformations like nevus flammeus. Clinical methods have been generally used to evaluate their effectiveness in many papers. OBJECTIVE: To evaluate the effectiveness of the laser therapy in nevus flammeus patients, we used reflectance spectrophotometry as a supportive objective method in addition to the clinical evaluation. METHODS: Thirty-two patients with definite nevus flammeus skin lesion, mainly on head and neck, were treated with flashlamp-pumped pulsed dye laser(SPTL-1b) at 8 week interval. Patients without previous treatment and the others with previous treatments were grouped separately to compare the influence of previous treatment to laser therapy. Erythema/Melanin indices were measured before and after laser therapy in both normal and lesional skin. Based on these indices, relative blanching effect were calculated. RESULTS: Clinically, they showed 58.6% improvement in their skin color in average and Erythema/Melanin indices measured on normal skins were 13.09+/-3.91 a.u. and 34.65+/-2.82 a.u.. Erythema indices measured on lesional skins were 26.07+/-10.26 a.u. and 20.73+/-8.81 a.u. in non-treated group and 2453+/-6.14 a.u. and 21.18+/-5.47 a.u. in pre-treated group, alternatively. Relative blanching effect in both groups were calculated as 35.9% and 31.6%, meaning no significant difference(p>0.3). Clinical evaluation and relative blanching effect showed good correlation(r=0. 691). CONCLUSION: Reflectance spectrophotometry can be useful in evaluating successful laser treatments in nevus flammeus patients. Reflectance measurements, an objective estimate of blanching, correlate well with the clinical results, and are helpful in monitoring and predicting the therapeutic outcome in dye laser treated patients.

Clinical Experience of Treatment in a Case of Sturge-Weber Syndrome with Bilateral Glaucoma

Sturge-Weber syndrome is a rare congenital anomaly characterized by angiomatosis of face, eye and leptomeninges and nevus flammeus is distributed along the trigminal nerve in face, often accompanying congenital glaucoma. We experienced a case of Sturge-Weber syndrome in an 11-year-old Korean girl of bilateral facial nevus flammeus with bilateral glaucoma treated by trabeculectomy and laser trabeculoplasty previously, but glaucomatous optic neuropathy progressed due to inadequate intraocular pressure control, and we could obtain successful result after trabeculectomy with mitomycin-C.

Histologic changes of nevus flammeus following copper vapor laser treatment / 대한피부과학회지

Nevus flammeus is a benign but cosmetically devascating congenital inalformation involving mature capillaries. The copper vapor laser is a therapeutic device which had been newly applied to this. Yellow copper vapor light is absorbed by the intraluminal oxyhemoglobulin mo ecules, leading to the destruction of blood vessels. This study was undertaken to evaluate the histobigic findings in a patient with nevus flammeus according to the sequential time after copper vapor laser therapy. The results were as followed, One hour after treatment, nonspecific damages to the epidermis and upper part of the dermis were observed. The specific damage to the vessels which showed thrombi formations and partial disruption of the vessel walls was prominent. One cay after treatment, degeneration of the epidermis and sepaiation of the dermoepidermal junction were apparent. Three days after treatment, extravasations of a small amount of erythrocytes and inflanimatory cell infiltrations were present, especially around the vessels. Seven days after treatment, the capillaries showed a deposition of fiorinoid material around themselves. Partial disappearance of the vessel walls was seen. There was hisi ologic evidence of the replacement of abnormal ectatic vessels by normal appearing vessels with small uminal diameters, surrounded by endothelial cells.

Phakomatosis Pigmentovascularis

Phakomatosis pigmentovascularis was first described in 1947 as a distinctive association of cutaneous hemangioma and pigmentary nevi by Ota et al. We describe a 7-year-old boy who, since birth, had three kinds of discolored patches over the various parts of the body: blue spots (dermal melanocytic nevi), reticulated reddish patches (nevus flammeus), and hypopigmented macules (nevus anemicus). No systemic disease was found.

A Case of Phakomatosis Pigmentovascularis with Eye Involvement / 대한피부과학회지

Phakomatosis pigmentova.scularis is a disease complex with dermal melanocyto sis such as nevus of Ota, nevus of Ito, or Mongolian spots and extensive hemangiomatous change such as nevus flammeus, which are associated with systemic organ involvement. We report a 23-year-old female, who showed bilateral nevus of Ota and nevus of Ito with widespread nevus flammeus and Mongolian spots since birth. She was also associated with megalocornea due to congenitol glaucoma and cataract.

Histology of Nevus Flammeus Following Argon Laser Treatment / 대한피부과학회지

We observed the histopathological findings in 16 patients with nevus flammeus according to the time sequence after argon laser therapy. The results were as follows : 1. Immediately after treatment There was nonspecific damage to the epidermis, upper part of the dermis and upper portion of the pilosebaceous unit to a depth of 0.4~0.5mm depth. The specific damage to the vessels, which showed thrombi formation and partial disruption of the vessel walls was seen to a depth of 0.8~0.9mm. 2. One week after treatment Crust was formed and the epidermis regenerated almost completely. The thrombi still persisted and there was partial disappearance of the vessel walls. 3. Four to 10 months after treatment The epidermis appeared normal except the rete ridge flattening. The upper dermis was diffusely fibrotic, with relatively few residual vessels, many of them with slit-like contour.

A Case Report of Klippel-Trenaunay-Weber Syndrome

The association of varicose vein, soft tissue and bony hypertrophy and cutaneous hemangi-oma of the port-wine variety confined to one extremity was first reported in 1900 by Klippel and Trenaunay, and then Weber. A case of Klippel-Trenaunay-Weber Syndrome with macrodactylia in a 2 months old male infant(dizygotic) is presented who was asmitted to B.N.U.H. with chief complaints of nevus fla-mmeus, swelling of the left lower extremity.