A family with pachyonychia congenita affecting the nails only

A family with pachyonychia congenita in which affected individuals showed nail involvement only is described. Pachyonychia congenita is a rare hereditary disorder inherited in an autosomal dominant manner. Various classifications of pachyonychia congenita have been suggested but none indicates nail involvement as a solitary finding.     

Macrocephaly-cutis marmorata telangiectatica congenita: A case report and review of salient features

Macrocephaly-cutis marmorata telangiectatica congenita is a recently recognized syndrome described mainly in the genetics literature. However, children with macrocephaly-cutis marmorata telangiectatica congenita are likely to present first to a dermatologist, with generalized cutis marmorata telangiectatica congenita as the main feature. These children are at risk of neurologic abnormalities and life-threatening complications. Therefore it is important for dermatologists to recognize this syndrome to monitor these children for potential complications. We report the case of a 2-year-old boy with macrocephaly-cutis marmorata telangiectatica congenita in association with dysmorphic facies, seizures, and facial and limb asymmetry, and we review the salient features of this syndrome.     

Pachyonychia congenita tarda

Pachyonychia congenita is a distinct hereditary disorder of keratinization, in which dystrophy of all nails is associated with palmoplantar keratoderma and other hyperkeratoses. Recently a late-onset type has been reported. We report a second family with late-onset pachyonychia congenita, showing a remarkable clinical heterogeneity. Furthermore, one patient demonstrated a number of associated hyperkeratoses not previously recognized. Acitretin proved useful in the treatment of this late-onset form of pachyonychia congenita.     

Dyskeratosis Congenita Associated with Elevated Fetal Hemoglobin, X-Linked Ocular Albinism, and Juvenile-Onset Diabetes Mellitus

An 11-year-old boy had dyskeratosis congenita, elevated fetal hemoglobin level, X-linked ocular albinism, and juvenile-onset diabetes mellitus. A review of the international literature revealed that elevated fetal hemoglobin has been noted in 15 reported cases of dyskeratosis congenita. It is a previously unrecognized, commonly associated finding in dyskeratosis congenita that may provide insight into the location and function of the gene for dyskeratosis congenita.     

Pachyonychia congenita with laryngeal obstruction

Pachyonychia congenita is a rare genodermatosis that can affect the larynx. Laryngeal obstruction is very unusual with only a few cases reported. A 2-year-old girl presented with typical clinical features of pachyonychia congenita shortly after birth. At age 9 months, following an upper respiratory infection, she developed stridor and hoarseness and was found to have severe laryngeal obstruction, which was felt to be secondary to pachyonychia congenita based on direct laryngoscopy and laryngeal biopsy. Leukokeratosis of her larynx was treated with CO(2) laser on three occasions, with improvement in her respiratory distress after each treatment. This report is the first case of pachyonychia congenita with laryngeal obstruction in which the gene mutation has been established (a deletional mutation in K6a), confirming that laryngeal obstruction can occur in PC-1.     

Incidental finding of cutaneous meningeal heterotopia in aplasia cutis congenita

Aplasia cutis congenita and cutaneous meningeal heterotopia are both rare congenital conditions that most commonly occur on the scalp and may appear clinically and histologically similar. A subtype of aplasia cutis congenita, membranous aplasia cutis congenita, and cutaneous meningeal heterotopia are both proposed to result from neural tube closure errors. However, neither non‐membranous nor membranous aplasia cutis congenita are known to occur together with cutaneous meningeal heterotopia in the same lesion. We report the incidental finding of cutaneous meningeal heterotopia within a lesion of aplasia cutis congenita.     

Cutis marmorata telangiectatica congenita

Cutis marmorata telangiectatica congenita is an uncommon vascular malformation composed of capillary and venous sized vessels. It presents with a distinct reticulated pattern that is reminiscent of physiologic cutis marmorata however skin lesions do not resolve with warming of the skin surface. It may have a localized or generalized pattern on the skin. Associated anomalies occur in individuals with cutis marmorata telangiectatica congenita the most commonly reported are limb asymmetry and the coexistence of other vascular birthmarks. Adams Oliver Syndrome and cutis marmorata telangiectatica congenital-macrocephaly syndrome are rare disorders that are associated with cutis marmorata telangiectatica congenita.     

Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita

Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.     

Pachyonychia congenita. A clinical, histological and microradiographic study with special reference to oral manifestations.

This paper rresents a clinical, histological and microradiographic study of three patients with pachyonychia congenita with special reference to oral manifestations. The patients, who are relatives, exhibited thickening of finger- and toe-nails, follicular keratosis, palmoplantar keratosis and hyperhidrosis, oral leukokeratosis, and natal teeth. It is stated in the discussion that natal teeth and oral leukokeratosis may constitute the earliest clinical manifestations of pachyonychia congenita and that they appear to accur earlier than nail lesions. When there is a hereditary disposition for pachyonychia congenita, it is important to inspect the oral cavity at an early stage.     

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.     

Identification of a novel mutation and a de novo mutation in DKC1 in two Chinese pedigrees with Dyskeratosis congenita

Dyskeratosis congenita (DKC) is a rare and fatal congenital syndrome characterized by the triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia, and the predisposition to bone marrow failure and malignancies. Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita. Here we report mutation analysis of two Chinese pedigrees with dyskeratosis congenita. The 15 coding exons of DKC1 and their flanking regions were amplified from genomic DNA by PCR. DNA sequencing and restriction endonuclease digestion were used for mutation detection. Transition mutation of 1226C-->T (P409L) found in the first pedigree is a novel mutation. In the second pedigree, the proband's mother phenotypically normal carried a de novo transition mutation of 1058C-->T (A353 V) in one allele, and transmitted the mutant allele to her two sons who had typical manifestations of dyskeratosis congenita.     

Duodenal atresia, biliary atresia, and intestinal infarct in truncal aplasia cutis congenita

A newborn boy with aplasia cutis congenita had biliary atresia, distal duodenal atresia, and a severe infarct of the intestine resulting in complete absence of the entire midgut. The boy died due to biliary atresia and severe short gut syndrome approximately 3 weeks after birth. While the association of duodenal atresia with aplasia cutis congenita has been described, the findings of biliary atresia and midgut atresia in association with aplasia cutis congenita have not been described previously.     

Aplasia cutis congenita in a defined population from northwest Spain

Aplasia cutis congenita is a rare condition characterized by congenital absence of the epidermis, dermis, and subcutaneous tissue. It may occur as an isolated defect or associated with other anomalies. This study sought to determine the frequency of this condition over a 10-year-period at the single hospital for a well-defined population. A literature review of potential mechanisms implicated in the development of this condition was also conducted. A retrospective review of all case records of patients diagnosed with aplasia cutis congenita between January 1994 and December 2003 at Hospital Xeral-Calde, in the Lugo region of northwest Spain was undertaken. During the period of study four patients were diagnosed with this condition. Three of them were of the gypsy race. These three had aplasia cutis congenita associated with epidermolysis bullosa and deformed nails. The incidence of aplasia cutis congenita in our region was 2.8 cases per 10,000 newborns. It was found that the incidence of this disorder in northwest Spain was similar to that described in the literature. Careful study due to the frequent association of aplasia cutis congenita with other congenital anomalies and a complete obstetric and family history of all affected individuals are required to identify possible specific teratogens, intrauterine infections, chromosomal abnormalities, or history of this condition among relatives.     

Cutis marmorata telangiectatica congenita and neonatal lupus

Cutis marmorata telangiectatica congenita is an uncommon congenital vascular anomaly that is characterized by persistent, reticulated, violaceous pigmentation. We describe a female infant with vascular lesions consistent with this entity who was born to a mother with previously diagnosed systemic lupus erythematosus. Antinuclear antibodies and anti-Ro/SSA antibodies were detected in both mother and infant, supporting a diagnosis of neonatal lupus. This presentation is consistent with the rarely reported association between neonatal lupus and cutis marmorata telangiectatica congenita that suggests the latter is part of the cutaneous spectrum of the former. A thorough maternal history and laboratory investigations should be considered for infants with cutis marmorata telangiectatica congenita and their mothers in order to rule out the presence of an underlying autoimmune disease.     

SCALP syndrome: sebaceous nevus syndrome, CNS malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus) with neurocutaneous melanosis: a distinct syndromic entity

Nevus sebaceus syndrome (SNS) is a constellation of nevus sebaceus with extracutaneous findings, including the ophthalmologic nervous, and musculoskeletal systems. Didymosis aplasticosebacea is a recently described entity consisting of aplasia cutis congenita and nevus sebaceus, implying twin spotting (didymosis). We describe a neonate with a nevus sebaceus on the scalp and a limbal dermoid on her left eye. Contiguous with the nevus sebaceus was a giant congenital melanocytic nevus and numerous areas of membranous aplasia cutis congenita. We propose the acronym SCALP (nevus sebaceus, central nervous system malformations, aplasia cutis congenita, limbal dermoid, pigmented nevus) to summarize the unique features of this case and review the two similar cases in the literature.     

Pachyonychia Congenita Type I Presenting with Subtle Nail Changes

Abstract:   Pachyonychia congenita type I is an autosomal dominant disorder where nail abnormalities are a constant feature and develop during childhood. We report here a family with pachyonychia congenita type I and very mild nail changes to underline that this diagnosis should be considered even in the absence of severe nail thickening.     

Symmetric aplasia cutis congenita associated with fetus papyraceus: report of two cases

We present two cases of neonates born with symmetric aplasia cutis congenita associated with intrauterine fetal demise of cotwins during the early second trimester. Fetus papyraceus resulting in aplasia cutis congenita is a rare association with many clinical presentations, including extratruncal symmetric lesions and small linear, arcuate, and triangular lesions when twin intrauterine demise occurs after the first trimester.     

Aplasia cutis congenita: a clinical review and proposal for classification

Aplasia cutis congenita is a condition in which localized or widespread areas of skin are absent at birth. Several distinct clinical subtypes occur, characterized by the location and pattern of skin absence, the presence of associated malformations, and the mode of inheritance. The disorder is seen most frequently on the scalp, often as a solitary lesion without other anomalies. Scalp lesions can be seen in association with limb reduction defects and in association with epidermal and organoid nevi. Lesions may overlie overt or occult embryologic malformations. A form of aplasia cutis congenita occurs in association with placental infarcts or the in utero death of a twin fetus. The condition may be associated with epidermolysis bullosa, specific teratogens or intrauterine infections, or it may occur in the presence of chromosomal abnormalities, ectodermal dysplasias, or other syndromes of malformation. A classification for aplasia cutis congenita is proposed.     

Aplasia cutis congenita with precancerous transformation - the first case. Why do these scars never develop invasive tumors?

The term aplasia cutis congenita characterizes a heterogeneous group of diseases which have in common a focal absence of the skin. The defect may be limited to the epidermis but often involves the full thickness of the skin including the underlying bone. At birth the lesions present as erosive patches and they heal rather rapidly with a residual scar. Although more than 200 publications on aplasia cutis congenita have appeared in the medical literature between 1966 and 1999, surprisingly no case of malignant degeneration has been described. We observed a 58-year-old male patient with aplasia cutis congenita who developed crusted changes within the scar over the past 10 years. Repeated biopsies over the years have always documented a precancerous lesion without solar elastosis. Invasion has never been observed in this patient. We hypothesize that for invasive malignancies dermal-epidermal interactions are necessary. Such a cell to cell communication seems to be impossible in patients with aplasia cutis congenita, as the dermal-epidermal unit is not developed. Aplasia cutis congenita might serve as an interesting model for further investigations on the importance of epidermal-dermal interactions.