Dermatoscopic aspects of the Microphthalmia with Linear Skin Defects (MLS) Syndrome

The association of microphthalmia and linear skin defects was named microphthalmia with linear skin defects syndrome (MLS) or MIDAS syndrome (microphthalmia, dermal aplasia, and sclerocornea), an X-chromosomal disorder manifesting mainly in females. We examined a female newborn with facial linear skin defects following the Blaschko lines. Computer tomography and ophthalmological examination confirmed bilateral microphthalmia. An interstitial microdeletion at Xp22.2, encompassing the entire HCCS gene, was identified. Dermatoscopic examination showed erythematous linear areas with telangectasias and absence of sebaceous glands, which appear as brilliant white dots. Vellus hairs were also absent in the red areas. Dermatoscopy could help to establish the diagnosis of MLS/MIDAS syndrome by confirming the aplastic nature of the lesions.     

Goltz综合征一例

患者,女,9岁。生后即见面部、躯干和四肢有多个红褐色斑、斑片及斑块,无自觉症状。部分线状或色素性斑沿Blaschko线分布,左小腿见数个脂肪性疝,肛周见多个乳头瘤状皮损,耳廓和牙齿畸形。组织病理示：真皮胶原纤维和弹力纤维缺如。根据临床和组织病理学表现诊断为Goltz综合征。     

Melanocyte stimulation in focal dermal hypoplasia with unusual pigmented skin lesions: a histologic and immunohistochemical study

Focal dermal hypoplasia (FDH) or Goltz syndrome is a rare genodermatosis transmitted in a dominant, X-linked mode. It is characterized clinically by atrophic skin lesions, multiple mucocutaneous papillomas, hyperpigmented linear skin lesions, and several skeletal and visceral anomalies. We followed over several years a female patient with FDH, who had the characteristic atrophic cutaneous lesions and periorificial papillomas, who developed at the periphery of atrophic lesions peculiar lentigo-like pigmented macules. Immunohistologically, increased melanin deposits within the epidermis and the dermis were seen, produced by stimulated epidermal melanocytes expressing the HMB-45 antigen. These findings further support the contention that cutaneous lesions of FDH may be progressive, and provide a physiopathologic basis for understanding the hyperpigmented lesions of FDH.     

Confocal and dermoscopic features of basal cell carcinoma in Gorlin–Goltz syndrome: A case report

Gorlin–Goltz (GS) syndrome is an autosomal dominant disease linked to a mutation in the PTCH gene. Major criteria include the onset of multiple basal cell carcinoma (BCC), keratocystic odontogenic tumours in the jaws and bifid ribs. Dermoscopy and reflectance confocal microscopy represent imaging tools that are able to increase the diagnostic accuracy of skin cancer in a totally noninvasive manner, without performing punch biopsies. Here we present a case of a young woman in whom the combined approach of dermoscopy and RCM led to the identification of multiple small inconspicuous lesions as BCC and thus to the diagnosis of GS syndrome.     

Xp22.3 microdeletion in a 19-year-old girl with clinical features of MLS syndrome

We describe a 19-year-old girl who has clinical features of microphthalmia with linear skin defects (MLS) syndrome caused by a microdeletion of Xp22.3. In addition to the classical ocular abnormalities and linear skin defects she has other features not previously described. She was previously reported in this journal in 1990 as poikiloderma congenitale, but her true diagnosis of an Xp22.3 microdeletion was clarified when fluorescent in situ hybridization (FISH) analysis indicated that one of her X chromosomes had a microdeletion including the KAL gene. We describe this patient with an Xp22.3 microdeletion to heighten awareness among dermatologists of this syndrome and to underscore the difficulties in diagnosing MLS syndrome.     

Revisiting histopathologic findings in Goltz syndrome

Goltz syndrome (focal dermal hypoplasia) is an X‐linked dominant disorder that is classically associated with yellowish papules representing fat herniation (superficial adipocytes). We report a series of three cases, with clinicopathologic correlation of biopsies from Blaschkoid streaks. A range of histopathologic features, including some underreported findings (increased papillary dermal blood vessels, decreased thickness of the dermis, and adipocytes high in the dermis), are reproducible and can strongly point to the correct diagnosis of Goltz syndrome.     

Microphthalmia with Linear Skin Defects Syndrome

Abstract: Microphthalmia with linear skin defects (MLS) or microcornea, dermal aplasia and sclerocornea (MIDAS) syndrome is a rare X‐linked‐dominant disorder. We present a patient with agenesis of corpus callosum, ocular abnormalities, and multiple skin defects. The cytogenetic studies of the MLS critical region (Xp22.2) were normal, but a skewed X‐chromosome inactivation pattern (85:15) was observed.     

新生儿Goltz综合征PORCN基因新发突变一例

【摘要】 目的 报道1例新生儿Goltz综合征及PORCN基因新发突变位点。方法 回顾性分析1例Goltz综合征新生儿的临床资料,采集患儿及父母外周静脉血,提取基因组DNA,全外显子组测序筛查患儿致病基因,Sanger测序法验证突变基因。结果 患儿女,出生后7 h因头皮缺损、面部、双膝关节内侧多发表皮缺损、左耳廓畸形、右手中指无名指并指、右足拇指二趾并趾、左足呈“龙虾爪”畸形就诊。基因检测显示,患儿PORCN基因第4外显子第514 ~ 521位插入了一段重复的TCCTTCCA片段（c.514_521dupTCCTTCCA）,导致第175号氨基酸由丝氨酸变为脯氨酸（p.S175Pfs*14）,并引起该蛋白的翻译在此后第14个密码子终止。患儿父母均未检测到此杂合突变。该患儿确诊为Goltz综合征。结论 Goltz综合征有多种表型,结合PORCN基因突变可确诊。c.514_521dupTCCTTCCA杂合突变为新突变。     

A Case of Goltz Syndrome Presenting as Congenital Incomplete Alopecia

A 5-year-old Japanese girl had had localized, incomplete hair loss on the scalp, minimal distichia, and a small papillomatous eruption on the right upper eyelid since birth. The diagnosis of Goltz syndrome was made by histological findings such as upward extension of the subcutaneous tissue to the papillary dermis and marked diminution in the thickness of the dermis, although typical linear atrophy-like eruptions and other mesoectodermal dysplasia were absent.     

Microphthalmia with linear skin defects: a case report and review

Microphthalmia with linear skin defects syndrome is an X-linked dominant disorder characterized by microphthalmia and other ocular anomalies as well as linear, jagged skin defects typically involving the scalp, face, neck, and upper trunk. Other associated characteristics include short stature, developmental delay, congenital heart defects, diaphragmatic hernia, agenesis of the corpus callosum, anencephaly, hydrocephalus, and seizures. Microphthalmia with linear skin defects syndrome is now known to be associated with a deletion of the X chromosome at Xp22. This is an area that has been found to include the HCCS gene, which encodes a holocytochrome c-type synthase believed to be critical in the regulation of apoptosis. We present a patient with classic clinical and genetic findings of MLS syndrome and discuss the primary characteristics and management of this disorder.     

Focal Dermal Hypoplasia (Goltz Syndrome): Report of Two Cases with Minor Cutaneous and Extraeutaneous Manifestations

Two women, ages 33 and 16 years, had focal dermal hypoplasia (Goltz syndrome) with unusual, minimal clinical manifestations. The lesions consisted of patchy, atrophic, scaly, telangiectatic macules arranged in a linear pattern along Blaschko's lines, involving the anterior and lateral aspects of both legs (patient 1) and the anterolateral aspect of the left leg (patient 2). Type I partial syndactyly involving the second and the third toes in both patients was also present. The clinical and histopathologic features and diagnostic difficulties of cases of this disorder with minimal cutaneous and extracutaneous manifestations are discussed.     

Focal Dermal Hypoplasia (Goltz Syndrome) with Horseshoe Kidney Abnormality

A 10-year-old girl had focal dermal hypoplasia (Goltz syndrome). She showed the characteristic skin manifestations, mental and physical underdevelopment, and facial, dental, skeletal, ophthalmologic, and urinary abnormalities. In addition, she had a horseshoe kidney abnormality.     

Focal dermal hypoplasia with exuberant fat herniations and skeletal deformities

Focal dermal hypoplasia or Goltz syndrome is a rare congenital and mesoectodermal dysplasia with multisystemic involvement. Although the genetic alterations responsible for focal dermal hypoplasia are not fully known, there is predominance in affected females, suggesting dominant X-linked inheritance. Besides the skin, other structures frequently involved are the skeletal system, eyes, teeth, hair, and nails. Skeletal abnormalities are predominantly observed in the hands and feet. We report a 9-year-old girl who had typical linear skin atrophy on the trunk, exuberant "fat herniations," several skeletal abnormalities, and exuberant "lobster claw" deformity. In addition, she had the typical longitudinal striations in femur metaphyses. With regard to family history, her mother had one male stillbirth with several deformities. This typical focal dermal hypoplasia patient is considered valuable in light of the affected male stillbirth and parents with nonaffected phenotypes that together provides evidence for mother-to-daughter spontaneous transmission.     

Reticulolinear aplasia cutis congenita of the face and neck: a distinctive cutaneous manifestation in several syndromes linked to Xp22

A distinct form of aplasia cutis congenita presenting as linear facial skin defects has been described under a variety of names as Xp deletion syndrome, MIDAS ( mi crophthalmia, d ermal a plasia and s clerocornea) syndrome, MLS ( m icrophthalmia and l inear s kin defects) and Gazali–Temple syndrome. The syndrome is lethal in males, and its severity in females varies from a relatively mild residual facial scarring with short stature to lethal developmental organ malformations. A new case with peculiar ultrastructural findings is presented. A review of the literature suggests that these associations represent a series of contiguous–gene syndromes.     

Multiple Epidermal Cysts in Lowe Syndrome

Lowe syndrome is a rare genetic disease that appears to cause various clinical symptoms involving the eye, nervous system, and kidney. While a mutation of the OCRL1 gene is known to be responsible for this syndrome, the exact pathophysiology remains unclear. Various multi-organ symptoms are characteristic of Lowe syndrome, but skin lesions have rarely been described. Recently, mechanisms for the association of Lowe syndrome and skin lesions have been proposed. We report this case of Lowe syndrome involving multiple epidermal cysts on the scalp in a 6-year-old male child.     

Goltz syndrome and PORCN mosaicism

Goltz syndrome, also known as focal dermal hypoplasia, is characterized primarily by ectodermal and mesodermal defects. Manifestations include cutis aplasia, dermal hypoplasia, papillomas, chorioretinal colobomas, absent/dysplastic teeth, and skeletal anomalies. Goltz syndrome is an X‐linked disorder due to mutations in PORCN, with a predominance of females affected. Germline mutations in PORCN are thought to result in embryonically lethality in males. We present a boy with a phenotype consistent with Goltz syndrome with low‐level mosaicism for a novel mutation in PORCN from peripheral blood (c.956dupA; p.Asn320GlufsX99).     

Focal Dermal Hypoplasia: Report of a Case with Myelomeningocele,Arnold–Chiari Malformation and Hydrocephalus with a Review of Neurologic Manifestations of Goltz Syndrome

Focal dermal hypoplasia (Goltz syndrome, Online Mendelian Inheritance in Man [OMIM] 305600) is a rare X‐linked dominant congenital disorder involving defects of mesodermal‐ and ectodermal‐derived structures. It is associated with mutations in the PORCN gene, a regulator of Wnt signaling proteins. The phenotype is highly variable, although all describe characteristic skin findings as a primary diagnostic feature. To date there are few case reports of focal dermal hypoplasia associated with central nervous system abnormalities. We report the second case of focal dermal hypoplasia associated with myelomenigocele, Arnold–Chiari malformation and hydrocephalus and the first in a male. Genetic testing identified a novel mosaic three base pair deletion within the PORCN gene (c.853_855delACG). This case highlights the importance of neurological evaluation in focal dermal hypoplasia and consideration of other syndromes more commonly associated with central nervous system abnormalities. In this report we summarize the literature on neurological manifestations in Goltz syndrome.     

Striation of bones in focal dermal hypoplasia: manifestation of functional mosaicism?

Striation of the metaphyseal regions of the long bones, a characteristic feature of the focal dermal hypoplasia syndrome, may be explained by functional X chromosome mosaicism. The following arguments are in favour of this hypothesis: (i) The striation of bones coincides with the zones of osteogenesis. (2) The skin lesions are distributed in a linear pattern as well. (3) The syndrome is probably inherited as an X-linked dominant trait. Thus, the linear pattern of both skin and bone lesions could be due to random X inactivation.     

Immunoreactivity for bcl-2 protein in cutaneous lymphomas and lymphoid hyperplasias*

The B-cell leukemia/lymphoma gene (bcl-2) produces a unique protein product (BCLP) that is believed to protect lymphoid cells from apoptosis. The bcl-2 gene is frequently rearranged in nodal follicular lymphomas as well as in diffuse lymphoproliferations, but has generally been regarded as most useful in the recognition of the former of these lesions. However, little is known regarding BCLP expression in cutaneous lymphoid infiltrates. Using an immunohistochemical technique and a monoclonal antibody (clone no. 124) the authors examined 67 examples of cutaneous lymphoid infiltrates – 31 cases of malignant lymphoma of the skin (MLS) and 36 examples of cutaneous lymphoid hyperplasias (CLH) – to determine if patterns of BCLP reactivity could distinguish CLH from MLS or primary from secondary involvement of the skin by malignant lymphoma. Fifty-eight per cent of MLS cases were BCL-positive, as were 33% of CLH. Three of four cases of follicular cutaneous lymphoma showed BCLP-positivity in neoplastic follicles, whereas similar structures in cases of CLH with a follicular pattern were BCLP-negative. Sixty per cent of primary MLSs and 57% of secondary lymphomas were reactive for BCLP. These data suggest that immunostains for BCLP are of little help in the separation of benign from malignant cutaneous lymphoid infiltrates, and that they are likewise incapable of separating primary from secondary MLS. BCLP immunostains may have a limited adjuvant diagnostic role in distinguishing reactive from neoplastic follicular lymphoid lesions of the skin.