Biomedical subjects
David de Berker
Publications and source records attributed to David de Berker.
The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia.
Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis.
Childhood nail diseases.
The diagnosis of pediatric nail populations is complicated because a large proportion of pediatric nail presentations involve parents bringing in their children with questions regarding nail appearance rather than the plain presentation of a disease or functional problem. Parents are concerned whether the nails are normal, if they are uncomfortable for the baby or child, if the nails will affect walking or other future function, or if the changes are of wider significance and suggest more sinister medical problems than are yet apparent. To address these concerns, the clinician needs a good grasp of what is normal.
Evaluation of a general practitioner with special interest service for dermatology: randomised controlled trial.
OBJECTIVE: To assess the effectiveness, accessibility, and acceptability of a general practitioner with special interest service for skin problems compared with a hospital dermatology clinic. DESIGN: Randomised controlled trial. SETTING: General practitioner with special interest dermatology service and hospital dermatology clinic. PARTICIPANTS: Adults referred to a hospital dermatology clinic and assessed by a consultant or the general practitioner with special interest service,. Suitable patients had non-urgent skin problems and had been identified from the referral letter as suitable for management by a general practitioner with special interest. INTERVENTIONS: Participants were randomised in 2:1 ratio to receive management by a general practitioner with special interest or usual hospital outpatient care. MAIN OUTCOME MEASURES: Primary outcomes were disease related quality of life (dermatology life quality index) and improvement in patients' perception of access to services, assessed nine months after randomisation. Secondary outcomes were patient satisfaction, preference for site of care, proportion of failed appointments, and waiting times to first appointment. RESULTS: 49% of the participants were judged suitable for care by the general practitioner with special interest service. Of 768 patients eligible, 556 (72.4%) were randomised (354 to general practitioner with special interest, 202 to hospital outpatient care). After nine months, 422 (76%) were followed up. No noticeable differences were found between the groups in clinical outcome (median dermatology life quality index score = 1 both arms, ratio of geometric means 0.99, 95% confidence interval 0.85 to 1.15). The general practitioner with special interest service was more accessible (difference between means on access scale 14, 11 to 19) and waited a mean of 40 (35 to 46) days less. Patients expressed slightly greater satisfaction with consultations with a general practitioner with special interest (difference in mean satisfaction score 4, 1 to 7), and at baseline and after nine months 61% said they preferred care at the service. CONCLUSIONS: The general practitioner with special interest service for dermatology was more accessible and preferred by patients than hospital outpatient care, achieving similar clinical outcomes. Trial registration ISRCTN31962758.
Pohl-Pinkus constrictions of hair following chemotherapy for Hodgkin's disease.
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A gene for pili annulati maps to the telomeric region of chromosome 12q.
Pili annulati (PA) is a rare hair shaft disorder characterized by discrete banding of hairs. We studied two families with PA in which the disorder segregated in an autosomal dominant fashion. All family members were clinically examined and hair samples were examined under the light microscope. In family G, of 19 individuals examined, ten were affected, over three generations. In family B, there were three affected individuals of seven examined over three generations. A genome-wide scan of family G revealed a maximum logarithm of odds (LOD) of linkage score of 3.89 at marker D12S1723 at the telomeric region of chromosome 12q. From one critical recombinant in family G, the locus was narrowed down to a 9.2 cM region between D12S367 and the end of chromosome 12q. In family B linkage at the telomeric region of chromosome 12q also revealed a maximum LOD score of 0.89 at marker D12S1723. A combined LOD score, assuming no locus heterogeneity between the families was 4.78. Frizzled 10, which is located within the region, was sequenced but we were unable to detect a mutation causing PA. This study, for the first time, identifies a genetic locus for PA.
Activation of Notch1 in the hair follicle leads to cell-fate switch and Mohawk alopecia.
The Notch signaling pathway has been shown to control cell-fate decisions during mouse development. To study the role of Notch1 in epidermal differentiation and the development of the various cell types within the mouse hair follicle, we generated transgenic mice that express a constitutive activated form of Notch1 under the control of the involucrin promoter. Transgenic animals express the transgene in the suprabasal epidermal keratinocytes and inner root sheath of the hair follicle, and develop both skin and hair abnormalities. Notch1 overexpression leads to an increase of the differentiated cell compartment in the epidermis, delays inner root sheath differentiation, and leads to hair shaft abnormalities and alopecia associated with the anagen phase of the hair cycle.
Managing common diseases of the nail.
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Progressive patterned scalp hypotrichosis, with wiry hair, onycholysis, and intermittently associated cleft lip and palate: clinical and genetic distinction from Marie Unna.
Marie Unna hereditary hypotrichosis has been described in over a dozen families since 1924. Features include scant or no eyebrows at birth, the development of firm wiry hair in the first few years of life followed by a progressive patterned scalp alopecia in the second or third decade. This is associated with generalized hypotrichosis of the body and the condition is nonsyndromic. We have identified a novel form of autosomal dominant ectodermal dysplasia that resembles Marie Unna hereditary hypotrichosis in a family of 23 members over four generations. Affected individuals have patterned hair loss and associated hair shaft dystrophy similar to that seen in Marie Unna hereditary hypotrichosis. It differs from Marie Unna hereditary hypotrichosis by an absence of signs of affectation at birth, relative sparing of body hair, distal onycholysis, and intermittent cosegregation with autosomal dominant cleft lip and palate. Linkage studies to the known Marie Unna locus at 8p21 near the Hairless gene were performed. Linkage analysis using markers D8S298, D8S560, D8S258, and D8S282 revealed significant exclusion of this locus (Z = -2.0 or lower) at theta = 0.1. This demonstrates that this novel ectodermal dysplasia is both phenotypically and genetically distinct from Marie Unna hereditary hypotrichosis.
Management of primary hyperhidrosis: a summary of the different treatment modalities.
Hyperhidrosis is a common and distressing condition involving increased production of sweat. A variety of treatment modalities are used to try to control or reduce sweating. Sweat is secreted by eccrine glands innervated by cholinergic fibers from the sympathetic nervous system. Primary hyperhidrosis most commonly affects palms, axillae and soles. Secondary hyperhidrosis is caused by an underlying condition, and treatment involves the removal or control of this condition. The treatment options for primary hyperhidrosis involve a range of topical or systemic medications, psychotherapy and surgical or non-surgical invasive techniques. Topical antiperspirants are quick and easy to apply but they can cause skin irritation and have a short half life. Systemic medications, in particular anticholinergics, reduce sweating but the dose required to control sweating can cause significant adverse effects, thus, limiting the medications' effectiveness. Iontophoresis is a simple and well tolerated method for the treatment of hyperhidrosis without long-term adverse effects; however, long-term maintenance treatments are required to keep patients symptom free. Botulinum toxin A has emerged as a treatment for hyperhidrosis over the past 5-6 years with studies showing good results. Unfortunately, botulinum toxin A is not a permanent solution, and patients require repeat injections every 6-8 months to maintain benefits. Psychotherapy has been beneficial in a small number of cases. Percutaneous computed tomography-guided phenol sympathicolysis achieved good results but has a high long-term failure rate. Surgery has also been shown to successfully reduce hyperhidrosis but, like other therapies, has several complications and patients need to be informed of these prior to undergoing surgery. The excision of axillary sweat glands can cause unsightly scarring and transthoracic sympathectomy (either open or endoscopic) can be associated with complications of compensatory and gustatory hyperhidrosis, Horner syndrome and neuralgia, some of which patients may find worse than the condition itself.
The physical basis of cosmetic defects of the nail plate.
Cosmetic defects of the nail cover a range of changes. Some are variants of normal which are considered unattractive, others are part of the normal ageing process and some changes are manifestations of local or systemic disease. Interpretation of these changes relies on recognition of the specific characteristics in question and an understanding of the anatomy and biology of nails. In many instances, therapies are limited and explanation of the changes represents one of the most useful contributions the professional can make to the affected individual. This article covers some of the most common cosmetic defects of nail involving colour, surface, brittleness and behaviour of surrounding tissues. Understanding of the physical basis of these defects is limited in many cases, but current thinking is recorded.
Subungual myxoid cysts: clinical manifestations and response to therapy.
BACKGROUND: Myxoid cysts located beneath the nail are very different from those within the nailfold and there is no established literature on their diagnosis and therapy. OBJECTIVE: Thirty-five cases of subungual myxoid cyst are described in which the diagnosis was confirmed by magnetic resonance imaging, surgical exploration, or both. METHODS: The clinical characteristics of all cases of subungual myxoid cysts confirmed in 3 specialist nail clinics are reported. Twenty cases were confirmed by magnetic resonance imaging. Histologic details were recorded in 4 cases. RESULTS: Thirty-four patients (22 female, 12 male) presented with a subungual tumor of the thumb (n = 25) or finger (n = 10). The 3 main clinical variables were color of the lunula, transverse nail curvature, and integrity of the nail. In 26 cases the lunula was discolored; it was red in 22 cases, blue in 3, and as part of a longitudinal leukonychia in one. Transverse curvature was increased in 29 cases and was normal in 5 cases; in one case the nail was destroyed. In 11 cases, the change in curvature led to lateral ingrowing. Surgery (n = 22), sclerosant (n = 1), and spontaneous discharge (n = 2) all resulted in resolution. Ten patients had no treatment. CONCLUSION: This study describes 35 subungual myxoid cysts having characteristic features that allow clinical diagnosis. They respond to a range of treatments.