Aplasia Cutis Research Articles

Aplasia cutis congenita with fetus papyraceus

We present a case of 8 h old newborn girl with symmetrical, stellate type of truncal aplasia cutis congenita. She was the survivor twin as the other fetus died at gestational age of 13 weeks and 5 days.

Prevalence of cutaneous skin lesions in neonatal intensive care unit: A single center study

Objectives: The prevalence of cutaneous lesions in newborns varies among different sex, and race. There are limited reports of skin lesions among Egyptians neonates. This study was conducted to determine the prevalence of different cutaneous lesions in newborns and evaluates the association between age, gender, maturity, route of delivery, birth weight, maternal disease, and different skin lesion. Patients and Methods: All of the subjects were healthy newborn infants, who were born between April 2013 and March 2014. They were enrolled and examined for cutaneous lesions by pediatrician and dermatologists. All patients were examined within the first 7 days of birth. Results: A total of 177 neonates were included in this descriptive prospective cohort study. Skin disorders were found in 132 neonates out of 177 (74.6%) of cases and 45 (25.4%) of cases were free of any skin disorder. Benign transient lesions of newborn were the most common category of neonatal skin disorders that were seen in 54 neonates (41% of all cases), followed in frequency by birth marks that were noticed in 45 neonates (34% of all cases). Napkin dermatitis was considered the third common category of neonatal skin diseases 20 (15.2%). Genodermatoses were only noticed in 3% of cases. Other (6.8%) of cases were [epidermolysis bullosae (1.5%), cutis aplasia congenital (2.3%), histocytosis X (1.5%), Suckling blisters (1.5%)]. Conclusion: Benign transient lesions of the newborn were the most common category of neonatal skin disorders, followed in frequency by birth marks. The prevalence of different pathological skin lesion was not common. The prevalence of the skin lesions of newborns are different in this study, these could be due to environmental factors, race, the age of the infant and the period of observation of the studied subjects.

Hamartome dendrocytaire dermique à type de médaillon : à propos d’un cas

Medaillon-like dermal dendrocyte hamartomas are rare congenital cutaneous lesions. They are present at birth as asymptomatic, benign, round, erythematous, well-circumscribed, atrophic patches. Typically, they have characteristic pliable, wrinkled surface; subtle telangiectases may also be appreciated. They are localized on the upper trunk or the neck. They may be misdiagnosed as atrophoderma, cutis aplasia, or anetoderma. Characteristic histologic findings include epidermal atrophy and the presence of CD34-positive spindle cell proliferation in the dermis. Little is known about the pathophysiology of medaillon-like dermal dendrocyte hamartomas. The main diagnosis pitfall is atrophic congenital dermatofibrosarcoma protuberance due to clinical and histological similarities. We emphasize that molecular studies to eliminate the t(17;22)(q22;q13) translocation of dermatofibrosarcomas may provide determinant elements for diagnosis in order to avoid unnecessary mutilating surgery. We present a case of medaillon-like dermal dendrocyte hamartoma with a local recurrence.

Aplasia cutis congenita: clinical management and a new classification system.

Aplasia cutis congenita is a rare, congenital disorder. In its severe phenotype, it is potentially life threatening. Its management and the timing of surgery remain controversial because of the risks involved with both conservative and surgical approaches. Most literature is based on case reports and very small case series because of the rarity of the disorder. The authors present their experience treating newborns with aplasia cutis congenita and its progressive development. Using a hospital registry, the authors found all cases of newborns diagnosed with aplasia cutis congenita during the years 2000 to 2013. Clinical data were gathered from hospital and clinic records, and photographs were obtained by the plastic surgery team. Twenty-two cases of aplasia cutis congenita were included in this study: 21 on the scalp and one on the foot heel. Eleven patients were male and 11 were female. Defect size ranged from 1 to 150 cm (average, 29 cm). Three patients died as a result of uncontrollable hemorrhage. Six patients underwent emergency coverage, one with allografts later replaced by split-thickness skin grafts and five by immediate split-thickness skin grafting. All of the patients who underwent immediate skin grafting survived and thrived. The authors emphasize the role of emergency split-thickness skin grafting in the treatment of large aplasia cutis congenita or ones with large veins or sagittal sinus exposure. The authors also present a practical, treatment-oriented classification that could assist physicians in estimating the severity and therefore prognosis of the disease and offer a treatment guideline. Therapeutic, IV.

Developmental abnormalities and nevi of the scalp

Unusual congenital or early-onset skin lesions on the scalp often pose a diagnostic challenge particularly as the clinical evaluation may be hampered by dense hair growth. Thus, this paper provides a concise review on developmental abnormalities and nevi with exclusive or predominant scalp localization. Aplasia cutis congenita occurs as an isolated finding, in association with genetic syndromes, nevi and anomalies or as a consequence of intrauterine trauma and teratogens. A hairless area with a narrow surrounding rim of hypertrichosis (hair collar sign) may point to occult cranial dysraphism, especially if accompanied by further suggestive signs as port-wine stains, large hemangiomas, dimples, congenital dermoid cysts, and sinuses. Many diverse entities may hide behind cutis verticis gyrata with the primary essential form being rare and representing a diagnosis of exclusion. In contrast to former belief, benign adnexal tumors arise in a nevus sebaceus considerably more often than basal cell carcinomas and other malignant epithelial tumors. Provided that tumor development is not suspected, excision of a nevus sebaceus nevus is indicated primarily for aesthetic-psychosocial reasons. However, surgical treatment is considerably easier in small children. Nevus sebaceus may be a cutaneous marker for several complex syndromes whereas nevus psiloliparus presents almost always in connection with encephalocraniocutaneous lipomatosis. Congenital melanocytic nevi of the scalp tend toward clinical regression, so that surgical intervention in large lesions should be carefully considered. In contrast, the threshold for excision of blue nevi and other conspicuous melanocytic nevi on the scalp should be low, especially since they are difficult to monitor.

English

INTRODUCTION: Aplasia Cutis Congenita (ACC) is a rare anomaly characterized by absence of portion of skin over localized or widespread area.1 ACC is most often a benign isolated defect,2 but it can be associated with other physical anomalies or malformation syndromes. More than 500 cases have been reported since it was first described, due to significant underreporting of this benign disorder, the precise frequency is unknown. Approximate incidence is 1:10,000 births,3 with no racial or sexual predilection. Scalp is the commonest location and is involved in almost 85% of cases rest 15% cases involve the non-scalp areas like forearms, knees, both sides of the trunk and neck in order of frequency.4,5 About 15% to 30% of the scalp involved patients have skull defects and defects of the dura. Involved areas are non-inflammatory and well demarcated and vary in size from 0.5 to 10 cm or larger. At birth lesions may have already healed and appear as an atrophic, membranous, bullous or parchment like scar with associated alopecia or may remain as a superficial lesion or erode deeply and occasionally involve the meninges.

Bullous aplasia cutis congenita with hair collar sign: A case report

Bullous aplasia cutis congenita with hair collar sign: A case report

Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

BackgroundKnobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. MethodsFour patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. ResultsWe identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. ConclusionsThis case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology—allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele.

Mutations in NOTCH1 Cause Adams-Oliver Syndrome

Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11families lacking mutations in the four genes with known roles in AOS pathology (ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de novo, in four unrelated probands. In a fifth family, we identified a heterozygous canonical splice-site variant (c.743-1 G>T) in an affected father and daughter. These variants were not present in 5,077 in-house control genomes or in public databases. In keeping with the prominent developmental role described for Notch1 in mouse vasculature, we observed cardiac and multiple vascular defects in four of the five families. We propose that the limb and scalp defects might also be due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations in NOTCH1 are the most common cause of AOS and add to a growing list of human diseases that have a vascular and/or bony component and are caused by alterations in the Notch signaling pathway.

Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia.

Variants in PORCN are a cause of Goltz-Gorlin syndrome or Focal Dermal Hypoplasia, an X-linked dominant disorder affecting heterozygous females and until now considered to be embryonic lethal in males. Exome sequencing was performed in a family in which two male siblings were characterized by microphthalmia and additional congenital anomalies including diaphragmatic hernia, spina bifida and cardiac defects. Surprisingly, we identified a maternally inherited variant in PORCN present in both males as well as in two female siblings. This represents the first finding of a PORCN variant in non-mosaic males affected with Goltz-Gorlin syndrome. The apparently asymptomatic mother showed extreme skewing of X-inactivation (90%), an asymptomatic female sibling showed skewing of 88%, and the second female sibling affected with cutis aplasia of the scalp showed X-inactivation considered within the normal range.

Historical Perspectives: Perinatal Profile: Forrest Hood Adams, MD: Pediatric Polymath

Forrest Adams is a descendant of Presidents John Adams (1735–1826) and John Quincy Adams (1767–1848), both of whom had long lives for the era into which they were born, which may indicate the role of genetics in his longevity. Both his grandparents and great grandparents lived into their 80s and 90s. Even as a medical student, he became interested in hereditary disorders and wrote an article before graduation, which was published approximately 1 year later, as the first article in his extensive bibliography. Indeed, the hereditary disorder that he described now bears his name, being the description of what became known as the Adams-Oliver syndrome. (1) This has to be a rare distinction for one so young at the time. The disorder consists of aplasia cutis congenita, in association with terminal transverse defects of the limbs and (in the first case he saw) a skull defect. The limb defects are not dissimilar to those seen with amniotic band syndrome. It is fair to say that Forrest Adams was (and is) a polymath (“a person of great learning in several fields of study”). Not only did he continue to be interested in genetics, he then spent time investigating infectious diseases, before moving on to pediatric cardiology and later to pulmonary physiology. As I found out in a recent telephone conversation, Dr Adams, at the age of 94 (going on 95), remembers in considerable detail many of the circumstances that led to his important contributions.⇓ Photograph taken in 2009 when receiving the Harold S. Diehl Award for outstanding professional contributions, from the University of Minnesota Medical School. Forrest Adams was born (in 1919) and raised in Minneapolis, Minnesota, where he went to medical school and graduated in 1943. Soon after this, his eponymous article was published and shortly after that he …

Fenotipo grave en dos medio hermanas con síndrome de Adams Oliver

Adams Oliver syndrome (AOS) is a highly variable entity with terminal transverse limb defects (TTLD) and aplasia cutis congenita (ACC) with a wide phenotypic spectrum. Several inheritance models have been observed; the most severe phenotype has been related to an autosomal recessive (AR) pattern of inheritance. OBJECTIVE. To present a family with two half siblings with a severe phenotype of Adams Oliver syndrome in which the mother was healthy. A 27 year-old woman was referred to the Genetics Department. Her previous girl presented acrania, constriction rings and terminal transverse limb defects. The present girl had occipital encephalocele, large scalp defects, aplasia cutis congenita, terminal transverse limb defects and bilateral cleft lip and palate. Autosomal dominant inheritance with reduced penetrance or gonadal mosaicism has to be considered in Adams Oliver syndrome with severe intracranial anomalies.

Extracellular O-linked β-N-acetylglucosamine: Its biology and relationship to human disease.

The O-linked β-N-acetylglucosamine (O-GlcNAc)ylation of cytoplasmic and nuclear proteins regulates basic cellular functions and is involved in the etiology of neurodegeneration and diabetes. Intracellular O-GlcNAcylation is catalyzed by a single O-GlcNAc transferase, O-GlcNAc transferase (OGT). Recently, an atypical O-GlcNAc transferase, extracellular O-linked β-N-acetylglucosamine (EOGT), which is responsible for the modification of extracellular O-GlcNAc, was identified. Although both OGT and EOGT are regulated through the common hexosamine biosynthesis pathway, EOGT localizes to the lumen of the endoplasmic reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT-independent manner. In Drosophila, loss of Eogt gives phenotypes similar to those caused by defects in the apical extracellular matrix. Dumpy, a membrane-anchored apical extracellular matrix protein, was identified as a major O-GlcNAcylated protein, and EOGT mediates Dumpy-dependent cell adhesion. In mammals, extracellular O-GlcNAc was detected on extracellular proteins including heparan sulfate proteoglycan 2, Nell1, laminin subunit alpha-5, Pamr1, and transmembrane proteins, including Notch receptors. Although the physiological function of O-GlcNAc in mammals has not yet been elucidated, exome sequencing identified homozygous EOGT mutations in patients with Adams-Oliver syndrome, a rare congenital disorder characterized by aplasia cutis congenita and terminal transverse limb defects. This review summarizes the current knowledge of extracellular O-GlcNAc and its implications in the pathological processes in Adams-Oliver syndrome.

Aplasia cutis congenita and limb anomaly: A case of non-scalp lesion

SUMMARY Aplasia cutis congenita is a rarely seen disease in which dermis, subdermal tissue and extremely rarely bone are absent. Significant number of cases are lost due to infections, electrolyte imbalance, and massive hemorrhage. In this report, we present a 2-day-old infant who had a wide aplasia cutis area on the right lower limb.

Adams-Oliver syndrome in a newborn infant

Adams-Oliver syndrome (AOS) is a rare multisystem disease of unknown aetiology, characterized by combination of aplasia cutis congenita of the scalp region and terminal limb anomalies. We present a case of a newborn infant with AOS: aplasia cutis congenita with defect of toes, wide bilateral parietal bone defect, partial agenesis of the corpus callosum and atrial septal defect. Skin defect of the scalp had spontaneously healed with cicatricial alopecia. Child’s mother was also born with aplasia cutis of the scalp, but no other associated anomalies. Neonates with AOS should be checked for other anomalies, and during their growth should be regularly followed-up by a team of specialists.

Aplasia cutis congenita with dystrophic epidermolysis bullosa: clinical and mutational study

Aplasia cutis congenita (ACC) has been associated with all clinical forms of inherited epidermolysis bullosa (EB), including dominant and recessive dystrophic EB (DDEB and RDEB). To date, only a few patients with DEB specifically combined with ACC have been described and genotyped and almost all cases represent dominant forms of the condition. The aim of this study was to describe new mutations of COL7A1 in patients with DEB and ACC and investigate possible genotype-phenotype correlations. Twenty-two patients with DEB and ACC were included among the 123 patients with DEB whose COL7A1 mutations have been identified in the Reference Centre in Nice. Seven patients presented a severe generalized RDEB phenotype (RDEB-sev-gen), while the other 15 suffered from milder phenotypes. We identified 28 mutations in COL7A1, of which nine are novel. Patients with severe phenotypes have mostly mutations leading to premature termination codon (PTC) and/or splice-site or missense mutations. Patients with the milder phenotypes have mostly glycine or arginine substitutions associated or not with other types of mutations. All amino acid substitutions fell within the carboxyl portion of the triple helix domain (THD) of collagen VII, close to the THD interruptions. Our findings suggest that ACC is a frequent manifestation in patients with DEB irrespective of the severity of the disease, and is due to leg rubbing in utero. In children with a moderate form of DEB with no or moderate skin fragility, a glycine substitution near the THD interruption domain of the collagen VII leading to thermolabile protein could explain this phenomenon.

Isolated terminal limb reduction defects: Extending the clinical spectrum of Adams–Oliver syndrome and ARHGAP31 mutations

Adams-Oliver syndrome (AOS; OMIM 100300) typically comprises a combination of congenital scalp defects and terminal transverse limb defects. Recently, mutations in ARHGAP31 and RBPJ have been found causing autosomal dominant forms of AOS. We describe a four-generation pedigree with isolated terminal limb defects and a truncating mutation in ARHGAP31. This finding underscores the relevance of sequencing ARHGAP31 in similar cases of isolated limb defects, irrespective of the presence of a complete AOS phenotype. We also highlight the variability of clinical features among mutation carriers, ranging from severe reduction defects to mild as well as clinically unaffected cases suggesting reduced penetrance.

Congenital Stigmatıc Alopecıas Associated with Occult Spinal Dysraphısm

Spinal dysraphism is one of the most frequent malformations, and is defined as a spectrum of congenital anomalies characterized by an incomplete fusion of the midline mesenchymal, bony, or neural elements of the spine.Both the skin and nervous tissue anomalies which originate from ectoderm may occur simultaneously. It can be occult or cystic. Occult forms (occult spinal dysraphism) are characterized by skin-covered lesions without exposed neural tissue. The diagnosis of the occult spinal disraphism is usually made based on a suspicion of the midline paraspinal skin lesions, mostly localized in the lumbosacral area such as subcutaneous lipomas, dermal sinuses, tails, sacral dimple, localized hypertrichosis, hyperpigmented lesions, hemangioma, mongolian spot, pigmentary nevus, and aplasia cutis congenita. Here we described four male babies with occult spinal dysraphism associated with unusual alopecic scalp lesions.

Calcified Scleral Choristoma in Organoid Nevus Syndrome Simulating Retinoblastoma

A child referred for management of retinoblastoma who alternatively had a calcified scleral choristoma as part of previously undiagnosed organoid nevus syndrome is described. A 31-month-old male infant with scalp alopecia was referred for retinoblastoma management after a calcified mass in his left eye was found. Ophthalmic examination revealed the mass was of choroidal or scleral origin, underlying the retina. The amelanotic circumpapillary mass extended superonasally in a geographic configuration and measured 14×12 mm. There was no subretinal fluid, hemorrhage, feeder vessels, or tumor seeding. Ocular ultrasonography confirmed a homogeneous calcified intraocular mass 3.1 mm in thickness. Enhanced depth imaging optical coherence tomography revealed that the lesion was located within the sclera compressing the overlying choroidal tissue. Further evaluation disclosed cutaneous aplasia cutis congenita with nevus sebaceous of Jadassohn. Magnetic resonance imaging disclosed an arachnoid cyst of the brain. Later, optical coherence tomography revealed the mass to be in the deep choroid or within the sclera. This constellation of ocular, cutaneous, and neurological features were suggestive of organoid nevus syndrome. At the 2-year follow-up, the findings were stable. The calcified choristoma of organoid nevus syndrome, located within the sclera in this case, has distinctive clinical features that differentiate this benign tumor from retinoblastoma.

Aplasia cutis in swine

The dermatopatologias are present in both pets and animal production. In the case of swine, are the most common skin diseases such as exudative epidermis (EE), sarcoptic mange and swine smallpox. However, there are also skin diseases affecting mainly pigs but are not reported as often. One is aplasia cutis or imperfectepiteliogênese, which is characterized by the absence of epidermis in some regions of the body of the piglet birth. Given that this disease presents as fortuitous cases within a farm, this work presents the occurrence of an event in a commercial farm in Viçosa (Minas Gerais, Brazil).