Somatic GNAQ mutation in different structures of port-wine macrocheilia.

BACKGROUND: Port-wine macrocheilia (PWM) involves a congenital, progressive capillary malformation that results in soft-tissue hypertrophy in the lips. Its aetiology has not yet been fully elucidated. OBJECTIVES: To investigate frequencies of GNAQ mutation in different tissues from patients with PWM, including skin, mucosa, gland and muscle, using samples obtained during cheiloplasty. METHODS: Targeted next-generation sequencing of GNAQ was designed and performed to assess DNA extracted from 80 different affected tissues from 20 patients with PWM. RESULTS: The GNAQ R183Q mutation was not detected in gland samples but was found in 90%, 95% and 95% of the skin, mucosal and muscle samples, respectively. The lowest levels of mutations were found in the glands (P < 0·001 vs. skin, mucosa and muscle), and levels were second lowest in the skin (P = 0·023 vs. mucosa; P = 0·012 vs. muscle). The mutation frequencies in mucosa and muscle were the highest and showed no statistically significant difference (P = 0·92). CONCLUSIONS: In patients with PWM, GNAQ was mutated in all tissues except for glands. PWM is congenital, and all tissue layers exhibit primary hypertrophy rather than acquired or partially related hypertrophy. Given the advantages of mucosal biopsy, including practicality, lack of scarring and rapid healing, GNAQ mutation in the lip mucosa may be a useful predictor for early-stage PWM in patients with port-wine stains affecting the lips.

The role of STK 11 gene testing in individuals with oral pigmentation.

Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant condition characterised by mucocutaneous pigmented lesions, gastrointestinal polyposis and a significant risk of cancer. Laugier-Hunziker syndrome (LHS) is a benign condition with similar dermatological features, but with no systemic complications. STK 11 gene testing allows clinicians to differentiate between these two disorders. This case report compares the dermatological similarities in four individuals with PJS or LHS and illustrates the potential benefit of genetic testing. There is > 90% likelihood of identifying a mutation in STK 11 if a patient fulfils the diagnostic criteria for PJS. Lifelong risk management is advised for these individuals with confirmed PJS. Diagnostic confirmation is important to provide rational management, in particular, endoscopic cancer surveillance, and psychological support. STK 11 testing can confirm those at risk of PJS, who require lifelong surveillance, and possibly release those with a simple dermatosis, such as LHS, from invasive and thus potentially harmful surveillance.

A family with radio-ulnar synostosis, scoliosis, and thick vermilion of lips: a novel syndrome or variant of Giuffrè-Tsukahara syndrome?

We report on a three-generation Chinese family presenting with a recognizable condition consisting of radio-ulnar synostosis, short stature, scoliosis, distinctive craniofacial features (thick vermilion to the lips, prominent eyes, and flat malar region), and a shortened and thickened femur neck. The inheritance of the trait was presumably autosomal dominant. The lack of microcephaly in the family suggested a variant of Giuffè-Tsukahara syndrome but could represent variability

Van der Woude syndrome: dentofacial features and implications for clinical practice.

BACKGROUND: Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS individuals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 individuals with VWS to facilitate its diagnosis. METHODS: A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort. RESULTS: The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%); unilateral cleft lip and palate (32%); submucous cleft palate (23%); and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected individuals. CONCLUSIONS: Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.

Isolated lower lip fistulas in Van der Woude syndrome.

Van der Woude syndrome (VWS) is a dominantly inherited disease of orofacial region. Characteristic features of this syndrome are bilateral lower lip sinuses along with cleft lip or palate deformity. However, isolated lower lip pits in VWS without any cleft syndrome is uncommon. Lip pits in VWS are usually asymptomatic; however, patients may complain of watery drainage and/or infection. In this report, asymptomatic isolated lower lip sinuses without any cleft syndrome in a patient and his father are presented.

A familial occurrence of lip anomaly.

Lip pits are among the rarest congenital deformities recorded. Initially reported in 1845, its familial occurrence has been reported just once. These developmental anomalies occur either as an isolated defect or in association with other developmental deformities, including cleft lip, cleft palate, or both. They may be located at the commissures of the lips or at the midline of the lower lip. Lip pits are often inherited as an autosomal dominant trait with variable penetrance. Our report of a family in which all of the 3 children (2 girls and 1 boy) and their father were involved is in concert with the latter statement.

Van der Woude syndrome: a report of two cases.

Van der Woude syndrome is a rare autosomal dominant condition with high penetrance and variable expression. It consists of a cleft lip and/or palate pits on the vermilion of the lower lip, and hypodontia. Two cases of congenital lip pits with cleft lip and alveolus and an isolated cleft palate are described to illustrate the variable presentation of the clinical features and the importance of early recognition of Van der Woude syndrome because of the genetic implications.

Van der Woude syndrome: a review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counselling and treatment.

Congenital pits of the lower lip constitute a rare developmental malformation, transmitted by an autosomal dominant mode, with considerable heterogeneity as regards the expression of the disorder. They are present in van der Woude syndrome (VWS), in which clefts of the upper lip and/or palate are often observed. Literature related to the various parameters associated with and relevant to the disorder is extensive. The purpose of this review is to cover, synthesize and categorize the existing knowledge into distinct entities, in order to facilitate understanding of the aetiopathogenesis of the malformation, its clinical manifestations and histological features, the epidemiology of the syndromic situation and the fundamental approach to an integral differential diagnosis. Special emphasis is given to the rationale underlying the treatment modalities that have been suggested, and the necessity for appropriate genetic counselling, as the disorder shows a high affinity with clefts and a familial type of occurrence.

Hereditary angioedema: a case report and literature review.

Hereditary angioedema is an autosomal dominant condition with a typical presentation of diffuse edematous, painless, and nonpitting swelling of the soft tissues. The disease manifests itself primarily in the extremities, face, airway, and abdominal viscera. Proper diagnosis and treatment are essential as this condition has the capacity of becoming life-threatening due to potential airway embarrassment. This case report demonstrates the complexity of diagnosing and treating hereditary angioedema. Hereditary angioedema often is overlooked on a differential diagnosis of patients suffering from diffuse swelling and/or abdominal discomfort. Nonetheless, the diagnosis of hereditary angioedema should be included when assessing patients who display the proper symptomology and familial history of the condition.

[T and B clonal populations in actinic prurigo, a photodermatosis]. / Poblaciones clonales de células T y B en prurigo actínico, una fotodermatosis.

Actinic prurigo (AP) is a chronic photodermatosis in which genetic and immunological factors has been implicated in the pathogenesis of the disease. This work was designed to investigate the existence of clonal populations of T and B lymphocytes in lesions of the labial mucosa and conjunctiva of patients with actinic prurigo. Genomic DNA of three patients with actinic prurigo and controls were analyzed in Southern blots using DNA molecular probes for the b subunit of the T-cell receptor for antigen (TCR beta) and for the heavy chain of immunoglobulin genes (lg-JH). Clonal rearrangements of T-cell receptor genes were detected in biopsy samples taken from the labial mucosa of two patients and of immunoglobulin genes in DNA extracted from the conjunctiva of a different patient. The presence of distinct clonal T or B lymphocyte populations in patients with actinic prurigo indicates that the immune system may play a relevant role in the pathogenesis of the disease.

[Variable expression of lower lip fistulas in Van der Woude syndrome]. / Variable Ausprägung der Unterlippenfisteln beim Van-der-Woude-Syndrom.

Eight families with the combination of cleft lip and/or cleft palate plus lower lip pits including their microforms were examined with the aim of characterization of microsymptoms. Hypodontia as a further symptom was also taken into consideration. Each of the symptoms was also noted separately in relatives of the patients and are to be considered as a genetic equivalent of the complete form of the autosomal-dominant inherited Van der Woude's syndrome. Knowledge of the variable expression of the basic gene is crucial for risk assessment in family counselling and also for distinguishing from clefts of other genesis with lower recurrence risk.

Linkage analysis of 5 novel van der Woude syndrome kindreds to 1q32-q41 markers further supports locus homogeneity of the disease trait.

van der Woude syndrome (vWS, MIM 119300) is a rare autosomal dominant clefting condition with cardinal features of mucous cysts (lower-lip pits) and clefts to the lip and/or palate. The vWS gene has been assigned to a locus in 1q32-q41 by linkage analysis and physical mapping. We have investigated 5 novel vWS families through probands attended for cleft lip and/or palate repair at the Department of Maxillofacial Surgery of Hôpital Trousseau, Paris, in order to tentatively refine the genetic map of the vWS region in 1q32-q41 and possibly identify unlinked pedigrees. Linkage analysis was carried out to 6 microsatellite markers (D1S249, D1S425, D1S491, D1S205, D1S414, D1S425), yielding a maximum cumulative LOD score of Z = 3.27 at theta = 0.00 for D1S245. The innermost four markers were found to be tightly linked to one another, with no evidence for recombination. Our results support linkage of vWS within a region of tightly linked markers and do not favour locus heterogeneity of the disease trait.

Familial cold urticaria--a rare cause of lip swelling.

Cold urticaria is an unusual condition characterised by wealing of the skin or mucous membranes following exposure to cold. This report describes a presentation with recurrent lip swelling.

Self-healing collodion baby: evidence for autosomal recessive inheritance.

Five spontaneously healing collodion babies were recorded in a large Swiss kindred. They all had consanguineous parents. Their distribution in the family indicates autosomal recessive inheritance. At birth they had the typical features of collodion babies. The collodion-like membrane was shed within the first month, leaving a slightly scaly skin for a few weeks. Thereafter the skin remained normal without any evidence of a disorder of cornification.

Natal teeth in monozygotic twins with Van der Woude syndrome.

The second monozygotic twin pair concordant for Van der Woude syndrome is reported. Clinical manifestations of this autosomal dominant clefting syndrome included bilateral lower lip pits, cleft lip, and cleft palate. Both sibs were found to have a natal tooth. No other cases of Van der Woude syndrome with this feature have been described previously. It is uncertain whether the presence of a natal tooth in this instance represents a low-frequency association of this disorder. However, it appears more likely that its occurrence was incidental, since natal teeth have been reported before in twin pairs as an isolated finding.