Aplasia cutis congenita: Evaluation of signs suggesting extracutaneous involvement

Specific clinical features of aplasia cutis congenita may indicate the presence of underlying cranial or cerebrovascular defects, allowing for early recognition and intervention. Most information about aplasia cutis congenita exists as individual case reports, with few large‐scale studies. We conducted a 7‐year retrospective chart review of 90 cases of aplasia cutis congenita and identified clinical characteristics including morphology, number of lesions, anatomic location, presence of hair collar sign, associated cutaneous features, histology, and imaging results. The anatomic location of the lesion (vertex, midline) (P = .01), presence of hair collar sign (P < .001), vascular stains (P < .001), and nodules (P = .007) were found to be strong clinical indicators of skull or cerebrovascular involvement.     

X‐linked dyskeratosis congenita presenting in adulthood with photodamaged skin and epiphora

Dyskeratosis congenita (DC) is a clinically and genetically heterogeneous multisystem bone marrow failure disorder of telomere maintenance, which may present with dermatological features. The main cause of mortality is bone marrow failure, often developing in the second decade of life, although pulmonary disease and malignancies such as squamous cell carcinomas (SCCs) may also prove fatal. We report the case of a 28‐year‐old man with X‐linked DC and confirmed DKC1 gene mutation. In addition to the classic triad of nail dystrophy, hyperpigmentation and oral leucoplakia, the patient had actinic keratosis (AK) and photodamaged skin, hitherto under‐recognized features of this condition. Awareness of the clinical presentation of DC is important, as accurate clinical and molecular diagnosis affords patients and their families genetic counselling, cancer prevention and screening measures, and planning for complications such as bone marrow failure.     

The keratin 16 null phenotype is modestly impacted by genetic strain background in mice

The type I intermediate filament keratin 16 (K16) is constitutively expressed in ectoderm‐derived appendages and is inducibly expressed in the epidermis upon barrier‐compromising challenges. Dominantly acting missense alleles in KRT16 are causative for pachyonychia congenita (PC), a genodermatosis involving debilitating palmoplantar keratoderma (PPK), nail dystrophy, oral lesions and, frequently, alterations in glands and hair. C57Bl/6;Krt16^‐/‐ mice develop oral lesions early after birth and PC‐like PPK lesions as young adults. These PPK lesions have a marked dysregulation of skin barrier‐related genes and innate immunity effectors (eg danger‐associated molecular patterns) and are preceded by oxidative stress secondary to hypoactive Nrf2 signalling. These molecular features are present in PPK lesions of PC patients. Here, we report that all components of the C57Bl/6;Krt16^‐/‐ mouse phenotype occur as well in the FVB strain background, albeit less severely so, a significant observation in the light of variations in the clinical presentation of individuals harbouring disease‐causing mutations in the KRT16 gene.     

Adams-Oliver syndrome with widespread CMTC and fatal pulmonary vascular disease

Abstract:  We report a neonate with cutis marmorata telangiectatica congenita and clinical features of Adams–Oliver syndrome in association with severe pulmonary vascular disease. We provide an overview of cutis marmorata telangiectatica congenita, distinguishing it from cutis marmorata, a common and benign physiologic cutaneous disorder seen in neonates. We highlight the need for thorough medical evaluation in cutis marmorata telangiectatica congenita to exclude associated congenital anomalies.     

Asymmetrical nonscalp aplasia cutis congenita: a case report

Aplasia cutis congenita or congenital absence of the skin is a rare and serious congenital disease; its etiopathogenesis remains unclear. In this condition, localized or widespread areas of skin are absent at birth. A newborn suffering from an unusual aplasia cutis congenita located asymmetrically on the nonscalp, without blistering, was presented. This patient was completely healed with conservative treatment.     

Nail manifestations of some important genetic disorders in children

There are some genetic disorders in which nail changes are the major feature, such as the nail patella syndrome and pachyonychia congenita. Nail abnormalities are a constant feature of other disorders such as hidrotic ectodermal dysplasia, dyskeratosis congenita, some forms of epidermolysis bullosa, and ichthyosis follicularis with alopecia and photophobia. Nail changes often occur in mal de Meleda, Papillon–Lefèvre syndrome, and the keratitis-ichthyosis-deafness (KID) syndrome and are an occasional feature in some other ichthyoses and in incontinentia pigmenti. In Goltz syndrome, nail changes can be supportive of the diagnosis in a case in which the other features are minimal or subtle. In Darier disease, nail changes may be the first sign of the disorder and lead to the diagnosis being made. Nail changes may occur in some conditions such as Apert syndrome and Adams–Oliver syndrome as a result of abnormalities of the distal phalanges.     

Collapse of the keratin filament network through the expression of mutant keratin 6c observed in a case of focal plantar keratoderma

Focal palmoplantar keratoderma (PPK) with severe pain is a hallmark of pachyonychia congenita, a rare autosomal dominant disorder involving PPK and hypertrophic nail dystrophy. Some families present focal PPK with either minimal or no nail changes. Dominant‐negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, KRT16 or KRT17, lead to pachyonychia congenita. However, the majority of families with focal PPK showing minimal or no nail changes do not harbor mutations in these genes. Recently, mutations of KRT6C were identified in families with focal PPK alone. Here, we report a 26‐year‐old Japanese man with focal plantar hyperkeratosis that developed at approximately 10 years of age with no palmar involvement and no nail alterations. We identified a missense KRT6C mutation c.1414G>A resulting in an p.Glu472Lys substitution, as reported in other Japanese patients. When the mutant keratin 6c protein is exogenously expressed in human HaCaT cells, a collapse of the keratin filament network is observed in a dose‐dependent manner, suggesting the mutation has a dominant‐negative effect on keratin filament network formation. The mutated residue is located at the helix termination motif of keratin 6c. The peptide sequence around this residue is highly conserved among type II, III and IV intermediate filament proteins. Glu to Lys mutations of the equivalent residue have been reported in a variety of inherited diseases, including neurodegenerative diseases, corneal dystrophy and skin disorders, suggesting that this residue is vital to keratin function.     

Die Ichthyosis congenita partim sanata

Zusammenfassung Auf Grund zweier alter und einer neuen Beobachtung wird unter Hinzuziehung einiger Literaturfälle versucht, eine eigene, wohl charakterisierte und aus diagnostisch-prognostischen Gründen wichtige Unterform der Ichthyosis congenita als Ichthyosis congenita partim sanata so vollständig wie zur Zeit möglich zu beschreiben und differentialdiagnostisch abzugrenzen.     

SCALP syndrome with a germline heterozygous DOCK6 mutation and somatic mosaic NRAS Q61R mutation

We present a case of SCALP syndrome, which was diagnosed in a male infant with the characteristic findings of sebaceous nevi, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and giant congenital melanocytic nevi, or pigmented nevi. We identified a germline compound heterozygous DOCK6 mutation and a somatic mosaic NRAS Q61R mutation in the giant congenital melanocytic nevus. This report will increase clinician awareness of SCALP syndrome and augment the literature in characterizing this rare syndrome, including its genetic background.     

Cutis marmorata teleangiectatica congenita (van Lohuizen syndrome)

Cutis marmorata teleangiectatica congenita is a rare birth defect of unknown etiology. The disease is characterized by reticular teleangiectasias and phlebectasias. Among the associated anomalies, hypoplasia of an affected extremity is most frequently observed. On the basis of two cases, the clinical features of cutis marmorata teleangiectatica congenita are described and the differential diagnosis discussed.     

Adams–Oliver Syndrome Type 2 in Association with Compound Heterozygous DOCK6 Mutations

Adams–Oliver syndrome (AOS) is a multiple congenital anomaly syndrome characterized by aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLDs). We present a case of type 2 autosomal recessive AOS associated with heterozygous mutations in the dedicator of cytokinesis 6 (DOCK6) gene, with characteristic findings of ACC, TTLD, intracerebral periventricular calcifications, and polymicrogyria.     

Dyskeratosis congenita associated with three malignancies

Dyskeratosis congenita is a rare inheritable disorder characterized by abnormalities of the skin, nails and oral mucosa. Aplastic anaemia resulting from bone marrow hypoplasia is a frequent cause of death. Squamous cell carcinoma developing from leukoplakia and visceral malignancies are other complications of the disease. We report here a case of dyskeratosis congenita in a man who developed three neoplasias of different systems over a period of many years. Squamous cell carcinoma and gastric adenocarcinoma manifested 17 years after the man was diagnosed with Hodgkin's disease.     

Autosomal dominant aplasia cutis congenita: report of a large Italian family and no hint for candidate chromosomal regions

Abstract We studied a three-generation pedigree in which seven individuals were affected by aplasia cutis congenita, a rare disorder characterized by the congenital absence of the epidermis, dermis and subcutaneous tissue of the vertex or occipital region. Accurate clinical and formal genetic analysis suggested that this family was affected by the autosomal dominant form of the disease, a hereditary condition due to mutations of an unknown gene. To define the map position of this locus, we performed linkage analysis on candidate chromosomes (long arm of chromosomes 1 and 12). Negative lod scores were obtained for all markers analysed and linkage with genes located in these chromosomal regions was excluded. Received: 3 March 1998 / Received after revision: 29 June 1999 / Accepted: 16 July 1999     

Generalized bullae in a young girl with KRT6A-related pachyonychia congenita

Pachyonychia congenita (PC) is a rare genodermatosis showing heterogeneity with five causative keratin genes (KRT6A, KRT6B, KRT6C, KRT16, or KRT17). Clinically, PC is characterized by hypertrophic onychodystrophy, painful palmoplantar keratoderma, oral leukokeratosis, and follicular hyperkeratosis. We describe an atypical case of PC in a young Chinese girl presenting with generalized bullae and identified a recurrent heterozygous missense mutation c.1406T > C (p.Leu469Pro) in KRT6A. This suggests that bullae may represent an important feature of KRT6A-related PC.     

Coats plus syndrome (cerebroretinal microangiopathy with calcifications and cysts‐1): A case report

We present a 6‐year‐old girl with skin hyperpigmentation, leukoplakia, and onychodystrophy, the classic mucocutaneous triad usually associated with dyskeratosis congenita. The patient also had premature graying of the hair, bone marrow failure, hepatitis, exudative retinopathy, osteopenia with multiple long bone fractures, and intracranial calcifications and brain cysts. Coats plus syndrome is a rare disease with a clinical and genetic overlap with dyskeratosis congenita. This disease is reviewed, with a focus on the pathogenesis of the genetic anomalies and its background as a telomere biology disorder.     

Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations

Pachyonychia congenita (PC), a rare autosomal‐dominant keratin disorder caused by mutations in keratin genes KRT6A/B, KRT16 or KRT17, is characterized by painful plantar keratoderma and hypertrophic nail dystrophy. Loss‐of‐function mutations in the filaggrin (FLG) gene underlie the most prevalent skin disorder of cornification, ichthyosis vulgaris (IV), which presents with generalized scaling and is also associated with atopic dermatitis. Recently, FLG mutations have been reported to increase phenotype severity of X‐linked ichthyosis and alopecia areata. We report a parent–child trio in which the mother and the son have PC and the father has IV. Both the mother and the son are carriers for the KRT16 mutation p.Leu132Pro. The son, who is much more severely affected than his mother, in addition carries the heterozygous FLG mutation p.R2447X, which was inherited from the father. This observation suggests that coinheritance of mutations in KRT16 and FLG may aggravate the PC phenotype and that FLG could serve as a genetic modifier in PC.     

先天性角化不良2例

先天性角化不良是一种罕见的多系统疾病，主要累及中胚层和外胚层，约80％以上的患者发生骨髓衰竭，并于早期死亡。报告2例患者，1例为22岁男孩，另1例为16岁女孩，均具有网状色素沉着伴毛细血管扩张及皮肤萎缩、甲营养不良、黏膜白斑等典型临床表现。男性患者伴有血液系统异常。     

Scottish Dermatological Society Abstracts Meeting: Inverness, June 1994

Pachyonychia congenita: another group of syndromes due to keratin gene mutations? Colin Munro, Lia kunkeler, Richard Morton, Mandy Hall, Steven Bryce, Simon Carter, Anthea Stevenson and Tom Strachan. Departments of Dermatology and Pathology, Southern General Hospital, Glasgow, and Department of Human Genetics, University of Newcastle upon Tyne     

Our experience with aplasia cutis congenita

Aplasia cutis congenita is a rare disorder characterized by developmental absence of skin on the scalp as multiple or solitary, noninflammatory, well demarcated, oval or circular 1- to 2-cm ulcers. The disease may be isolated or associated with anomalies of the skin, eyes, ear-nose-neck and limbs, developmental defects of the cardiovascular, gastrointestinal, genitourinary and central nervous systems, and malformation syndromes such as chromosomal abnormalities, Adams-Oliver syndrome, Bart's syndrome, and Johanson-Bilzzard syndrome. In this article, five newborn infants with aplasia cutis congenita (one associated with Adams-Oliver syndrome and another concomitant with Bart's syndrome) are reported because of their rare presentation in the literature.