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Sclerosteosis is a high bone mass disorder, caused by pathogenic variants in the genes encoding sclerostin or LRP4. Both proteins form a complex that strongly inhibits canonical WNT signaling activity, a pathway of major importance in bone formation. So far, all reported disease-causing variants are located in the third β-propeller domain of LRP4, which is essential for the interaction with sclerostin. Here, we report the identification of two compound heterozygous variants, a known p.Arg1170Gln and a novel p.Arg632His variant, in a patient with a sclerosteosis phenotype. Interestingly, the novel variant is located in the first β-propeller domain, which is known to be indispensable for the interaction with agrin. However, using luciferase reporter assays, we demonstrated that both the p.Arg1170Gln and the p.Arg632His variant in LRP4 reduced the inhibitory capacity of sclerostin on canonical WNT signaling activity. In conclusion, this study is the first to demonstrate that a pathogenic variant in the first β-propeller domain of LRP4 can contribute to the development of sclerosteosis, which broadens the mutational spectrum of the disorder.

Bone remodelling is a complex mechanism regulated by osteoclasts and osteoblasts and perturbation of this process leads to the onset of diseases, which may be characterised by altered bone erosion or formation. In this review, we will describe some bone formation-related disorders as sclerosteosis, van Buchem disease, hypophosphatasia and Camurati-Engelmann disease. In the past decades, the research focused on these rare disorders offered the opportunity to understand important pathways regulating bone formation. Thus, the identification of the molecular defects behind the etiopathology of these diseases will open the way for new therapeutic approaches applicable also to the management of more common bone diseases including osteoporosis.

Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) is an extremely rare autosomal recessive limb abnormality characterized by the fusion of third and fourth fingers. To date, only homozygous missense and frameshift mutations have been reported in BHLHA9 associated to MSSD. In this study, we report a patient who presented with clinical and radiological features of MSSD. A customized skeletal dysplasia NGS panel revealed the presence of two novel compounds heterozygous variants in BHLHA9: NM_001164405.1: c.[226A>T][269G>C]; p.[(Lys76*)][(Arg90Pro)]. Thus, this is the first case of MSSD in a nonconsanguineous family., (© 2020 Wiley Periodicals, Inc.)

Although congenital hand anomalies associated with finger nubbins may be produced by amniotic band disruption sequence (ABDS), symbrachydactyly should be considered in the differential diagnosis. ABDS usually affects more than one limb but symbrachydactyly largely is limited to one upper extremity, and has five distinct clinical presentations: short-fingered, atypical cleft, monodactylous, peromelic, and a forearm proximal transverse deficiency. This article discusses the diagnosis of symbrachydactyly compared with ABDS and outlines plans for managing patients with symbrachydactyly.

Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single affected individual; in another, biopsy of skin lesions showed features of trichoblastoma. The combination of asymmetric clinical features, patchy skin manifestations, and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving hedgehog (Hh) signaling. Here, we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO (c.1234C>T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that transduces Hh signaling. We identified eight mutation-positive individuals (two of whom had not been reported previously) with highly similar phenotypes and demonstrated varying amounts of the mutant allele in different tissues. We present detailed findings from brain MRI in three mutation-positive individuals. Somatic SMO mutations that result in constitutive activation have been described in several tumors, including medulloblastoma, ameloblastoma, and basal cell carcinoma. Strikingly, the most common of these mutations is the identical nonsynonymous variant encoding p.Leu412Phe. Furthermore, this substitution has been shown to activate SMO in the absence of Hh signaling, providing an explanation for tumor development in CJS. This raises therapeutic possibilities for using recently generated Hh-pathway inhibitors. In summary, our work uncovers the major genetic cause of CJS and illustrates strategies for gene discovery in the context of low-level tissue-specific somatic mosaicism., (Copyright © 2016. Published by Elsevier Inc.)

During the past 15 years there has been an expansion of our knowledge of the cellular and molecular mechanisms regulating bone remodeling that identified new signaling pathways fundamental for bone renewal as well as previously unknown interactions between bone cells. Central for these developments have been studies of rare bone disorders. These findings, in turn, have led to new treatment paradigms for osteoporosis some of which are at late stages of clinical development. In this article, we review three rare skeletal disorders with case descriptions, pycnodysostosis and the craniotubular hyperostoses sclerosteosis and van Buchem disease that led to the development of cathepsin K and sclerostin inhibitors, respectively, for the treatment of osteoporosis.

Unlabelled: Various surgical techniques are described for separation of syndactylies leading to good results. However, the use of standard techniques is limited in complex syndactylies with extensive bony fusion and tight soft tissues. The aim of this study was to assess the outcomes of a two-stage procedure involving progressive soft tissue distraction prior to syndactyly release. Between 1996 and 2012 we treated 168 complex syndactylies with this technique. The main indications were syndactylies in Apert syndrome. The digits were distracted through an external fixator at 0.5 mm/day. Distraction of 15-25 mm was achieved. Soft tissue distraction provided additional skin, a wider nail matrix and more bone in the form of callus. Thus subsequent modelling of the fingertips was improved, especially if they were closely fused. This technique facilitates treatment of complex cases and improves aesthetic outcome., Level of Evidence: Therapeutic IV., (© The Author(s) 2015.)

Fraser syndrome is a rare genetic disorder characterized by cryptophthalmos, syndactyly and laryngeal atresia. Although laryngeal webs occur uncommonly, they are the main cause of death in the first week of life in these patients. In this paper, we report two cases of Fraser syndrome with laryngeal webs. One of them was a twelve-year-old girl, primarily diagnosed with a supraglottic laryngeal web. In the course of treatment, a second web was also identified at the level of vocal cords, which is to our knowledge the first case of Fraser syndrome with two laryngeal webs in different levels., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Amniotic band syndrome is a rare congenital disorder. The authors report the first cases documented at Souro Sanou University Hospital in Bobo-Dioulasso (CHUSS) in 2 male new borns. The malformations found at birth, were worn only on limbs and were in the form of skin furrow necking with a major lymphedema downstream. In both cases, the constriction furrow at member pelvic was associated with a club foot and a pseudosyndactyly in one case. Surgical treatment consisted of a section of the constrictor ring and a Z-plasty. The functional outcome was satisfactory with the acquisition of a plantar support for both children. Through these two observations, epidemiological, diagnostic, and particularities of the management of this condition are discussed in the Burkina-Faso.

Several functionally limiting sequelae can follow deep thermal injury to the hand. Despite appropriate initial management, contractures are common. Whereas acute burn care is often managed by multidisciplinary, specialized burn units, postburn contractures may be referred to hand surgeons, who should be familiar with the patterns of burn contracture and nonsurgical and operative options to improve function and expected outcomes. The most common and functionally limiting sequelae are contractures of the webspace, hand, and digits. Webspace contractures and postburn syndactyly are managed with scar excision and local soft tissue rearrangement or skin grafting. The burn claw hand presents as extension contracture of the metacarpophalangeal joints and flexion contractures of the proximal interphalangeal joints. The mainstays of management of these contractures include complete surgical excision of scar tissue and resurfacing of the resultant soft tissue defect, most commonly with full-thickness skin grafts. If scar contracture release results in major exposure of the tendons or joints, distant tissue transfer may be required. Early motion and rehabilitative modalities are essential to prevent initial contracture formation and recontracture after surgical release., (Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Syndactyly or webbed fingers is one of the most common congenital malformations of the upper extremities, but it comprises few new cases annually. The purpose of treatment is to enhance hand function., Method: The article is based on current text books and literature searches in PubMed as well as the authors' clinical experience within this field., Results: The purpose of surgical treatment is to separate the fingers and reconstruct a webspace. It is difficult to indicate exact treatment results because of large variations in the extent of the deformity. For syndactyly involving only soft tissue (simple syndactyly), a good functional result is achieved with a less than 10% risk of complications. Syndactyly where also the bones have fused (complex syndactyly) or where there is additional bone formation between two digital rays (complicated syndactyly), gives a poorer functional outcome and a higher risk of complications. Gradual stretching of the tissue using a distraction device enables separation of fingers one was previously reluctant to separate., Interpretation: It should be possible to expect safe separation with a good and independent function of the fingers with surgical treatment. The parents should be informed that the surgical treatment is a reconstructive procedure that may require secondary corrections.

Congenital cytomegalovirus (CMV) infection is the most common cause of intrauterine infection. It affects the central nervous system and causes microcephaly, hydrocephalus, mental retardation, hearing disorder, chorioretinitis and rarely finger anomalies. We present the case of a 4-month-old girl with an agenesis of the middle finger and syndactyly of the fourth and fifth fingers as a result of congenital CMV; this is the first such case in the literature. Here, congenital CMV infection is examined along with finger anomalies.

Methods for generating loss-of-function mutations, such as conventional or conditional gene knockout, are widely used in deciphering gene function in vivo. By contrast, inducible and reversible regulation of endogenous gene expression has not been well established. Using a mouse model, we demonstrate that a chimeric transcriptional repressor molecule (tTS) can reversibly inhibit the expression of an endogenous gene, Nmyc. In this system, a tetracycline response element (TRE) artificially inserted near the target gene's promoter region turns the gene on and off in a tetracycline-inducible manner. Nmyc(TRE) mice were generated by inserting a TRE into the first intron of Nmyc by the knockin technique. Nmyc(TRE) mice were crossed to tTS transgenic mice to produce Nmyc(TRE/TRE): tTS embryos. In these embryos, tTS blocked Nmyc expression, and embryonic lethality was observed at E11.5d. When the dam was exposed to drinking water containing doxycycline (dox), normal endogenous Nmyc expression was rescued, and the embryo survived to birth. This novel genetic modification strategy based on the tTS-dox system for inducible and reversible regulation of endogenous mouse genes will be a powerful tool to investigate target genes that cause embryonic lethality or other defects where reversible regulation or temporary shutdown of the target gene is needed.

The keloid scar is a fibrous skin tumor, intradermal, and exuberant. It is commonly found on the glabrous skin. The keloid of the palms and soles are rare. Small series are reported in English literature. The authors report a case of large keloids located on both palms and soles, within a context of keloid disease, in a man of 37 years. On the left hand, the keloid scar caused a partial syndactyly IV-V. Large keloid tumors occupied the inner edge and, weight-bearing areas of both feet. These tumors rendered wearing of shoes impossible and interfered with walking. The treatment consisted of total excision of palmar and plantar keloid tumors. The residual defects were covered by a total skin graft taken from the suprapubic region. The results were satisfactory aesthetically, functionally and psychosocially., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The authors describe a case of Cenani-Lenz syndrome, in a 3-month-old girl of non-consanguineous parents of Afghani origin. Digital anomalies consist of sandactyly of the fingers of both hands, disorganised phalanges more severe involvement of the left side without radioulnar synostosis. Although our patient lacks facial dysmorphic features reported previously. The cases of patients with CLS need to be carefully evaluated and described to determine if there is distinctive accompanying facial phenotype.

The underlying genetic abnormalities of epidermolysis bullosa (EB) cause destabilization at the dermo-epidermal junction. Patients with EB characteristically are subject to blistering following relatively minor trauma (the Nikolsky sign), and suffer from ulcers and erosions in all areas subject to persistent or repeated friction, such as the hand. Hand deformities occur in most patients with dystrophic EB (DEB), and include adduction contractures of the first web space, pseudosyndactyly, and flexion contractures of the interphalangeal, metacarpophalangeal, and wrist joints. All structures in the hand may be involved. The severity of the deformity worsens with age, and surgical correction becomes increasingly difficult. Recurrent deformity occurs within 2 to 5 years. Meticulous skin care and the use of well-fitted splints supervised within a multidisciplinary team setting are essential. To date there is no strong evidence base on which to plan surgical treatment of the hand in DEB., (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.)

The release of postburn contractures in the hand is one of the most commonly performed procedures in burn injuries. Various local flaps have been described for release of severe postburn contractures. As the largest burn center covering north and northwest of Iran, we always needed acceptable reliable methods to reconstruct postburn syndactyly and make it as a standard treatment. We used double Z-plasties for the first web in severe contractures (23 patients) and V-M plasties for the second, third, and fourth webs and minor first web contractures (V for the dorsal aspect and M for the volar aspect of the webs). A total of 50 patients from September 2005 to June 2007 with 130 web contractures were operated. Their age ranged from 1 to 75 years. In a 1-year follow-up, all of the patients had good mobility of the fingers with no recurrence. Three cases of necrosis of tip of Z-plasties and 2 cases of necrosis of tip of V-M plasties occurred which were under 3 mm and resolved gradually. Double Z-plasty in first web and V-M plasty in second to fourth webs are considered good choices for release and reconstruction of postburn syndactyly. They are straightforward in technique and can be carried out with little complications.

Objective: To explore the genetic and environmental factors related to the development of polydactyly and syndactyly, and to provide evidence for prevention on birth defects., Methods: A hospital-based case-control study was conducted. 111 cases and 222 controls were interviewed with standardized questionnaires. Logistic regression models were used to select risk factors., Results: Research data through univariate analysis showed that the occurrence of polydactyly and syndactyly were associated with educational level, annual average income per family member, meat and egg intake during early pregnancy, family heredity history, exposure to hazardous substance before pregnancy, serious pregnant reaction etc. of the pregnant women. As shown in multivariable logistic model, some factors, including annual average income of per family member (OR = 0.240), meat and egg intake during early pregnancy (OR = 0.182), could reduce the risk of the development of polydactyly and syndactyly. Other factors including family heredity history (OR = 10.187), exposure to hazardous substance before pregnancy (OR = 3.029), could increase the risk of developing polydactyly and syndactyly. The attributable risks (%) of family heredity history and exposure to hazardous substance before pregnancy were 90.18% and 66.99% respectively., Conclusion: Genetic factor was the leading cause on the development of polydactyly and syndactyly. In addition, environmental factors, such as family economic condition, nutritional status during early pregnancy and working condition before pregnancy were associated with the development of polydactyly and syndactyly.

Andersen-Tawil syndrome includes a clinical triad consisting of periodic paralysis, cardiac arrhythmia, and usually mild but diagnostically useful dysmorphic features. This potassium channelopathy is due to mutation of the KCNJ2 gene encoding the protein Kir 2.1. The main muscular manifestation is periodic paralysis, usually of the hypokalemic type. Muscle biopsy may reveal tubular aggregates or be normal, as in our patient. Cardiac manifestations are variable and may include a long QT syndrome, premature ventricular contractions, complex ventricular ectopy, and polymorphic or bidirectional ventricular tachycardia. Imipramine therapy had a positive effect on arrhythmia in our patient. Dysmorphic features provide a diagnostic clue but may be difficult to identify and should thus be methodically sought. Clinical expression is variable, even within the same family. Since the culprit gene KCNJ2 was identified, locus heterogeneity has been shown in Andersen-Tawil syndrome. Kindreds without KCNJ2 mutations are clinically indistinguishable from those with mutations. Kir2.1 is an inward rectifier K+ channel with important roles in maintaining membrane potential and during the terminal phase of cardiac action potential repolarization. Several studies show a dominant negative effect of KCNJ2 mutation on Kir 2.1 channel function.

Curry-Jones syndrome (OMIM #601707) is a rare multiple malformation disorder of unknown etiology, associated with brain and skull abnormalities, polysyndactyly, and defects of the eyes, skin and gastrointestinal tract. We report on two new cases of Curry-Jones syndrome with previously unreported features, including benign and malignant neoplasms. The first patient had typical features of Curry-Jones syndrome as well as multiple intra-abdominal smooth muscle hamartomas and trichoblastoma of the skin. The second patient was born with occipital meningoceles and developed a desmoplastic medulloblastoma. Routine lymphocyte karyotype, GLI3 gene analysis and Patched (PTCH) gene analysis on both patients and chromosome microarray analysis on the first patient were normal. We review the previously reported cases of Curry-Jones syndrome and compare our patients' findings. In view of the association of trichoblastoma with basal cell carcinoma and desmoplastic medulloblastoma with nevoid basal cell carcinoma syndrome (NBCCS) and PTCH mutations, we hypothesize that Curry-Jones syndrome is caused by malfunction of an element in the sonic hedgehog pathway., (2008 Wiley-Liss, Inc.)

Wnt signaling pathways are regulated both at the intracellular and extracellular levels. During embryogenesis, the in vivo effects of the secreted frizzled-related protein (Sfrp) family of Wnt inhibitors are poorly understood. Here, we show that inactivation of Sfrp2 results in subtle limb defects in mice with mesomelic shortening and consistent shortening of all autopodal elements that is clinically manifested as brachydactyly. In addition, there is soft-tissue syndactyly of the hindlimb. The brachydactyly is caused by decreased chondrocyte proliferation and delayed differentiation in distal limb chondrogenic elements. These data suggest that Sfrp2 can regulate both chondrogenesis and regression of interdigital mesenchyme in distal limb. Sfrp2 can also repress canonical Wnt signaling by Wnt1, Wnt9a, and Wnt4 in vitro. Sfrp2-/- and TOPGAL/Sfrp2-/- mice have a mild increase in beta-catenin and beta-galactosidase staining, respectively, in some phalangeal elements. This however does not exclude a potential concurrent effect on non-canonical Wnt signaling in the growth plate. In combination with what is known about BMP and Wnt signaling in human brachydactylies, our data establish a critical role for Sfrp2 in proper distal limb formation and suggest SFPR2 could be a novel candidate gene for human brachy-syndactyly defects., ((c) 2008 Wiley-Liss, Inc.)

The Greig cephalopolysyndactyly syndrome (GCPS) is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1-9/1,000,000). The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome. Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above) and a GLI3 mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform. Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. Treatment of the disorder is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations. The prognosis for typically affected patients is excellent. There may be a slight increase in the incidence of developmental delay or cognitive impairment. Patients with large deletions that include GLI3 may have a worse prognosis. The Article is a work of the United States Government. Title 17 U.S.C 5 105 provides that copyright protection is not available for any work of the United States Government in the United States. The United States hereby grants to anyone a paid-up, nonexclusive, irrevocable worldwide license to reproduce, prepare derivative works, distribute copies to the public and perform publicly and display publicly the work, and also retains the nonexclusive right to do all of the above for or on behalf of the United States.

Significant hand burns frequently result in dorsal and/or palmar neosyndactyly despite appropriate wound care, excision/grafting, and occupational therapy. Patients often develop limited abduction, tethered flexion/extension, intrinsic tightness, and inversion of the web space. We present a new technique for neosyndactyly release "The Cross Incision Plasty." We performed a retrospective review of 15 patients who underwent 35 web space reconstructions by a single surgeon from January 2004 to February 2007. The cross incision plasty was developed before the study period with the following goals: to use local tissue, negate the need for a skin graft, and permit early range of motion. Combined with longitudinal and transverse releases, the cross incision plasty uses the four finger flaps, harvested from each sidewall of both proximal phalanges with 90-degree angle. The cross incision plasty simultaneously deepens and widens the web space while correcting the angle of inclination. Fifteen patients (mean age: 13.3 years; range: 3-24 years) underwent 35 cross incision plasties after burn injury. No complications such as infection, flap loss, dehiscence, nerve injury, or recurrent contracture were seen in the cross incision plasty group. All patients improved function (mean follow-up: 15.2 months; range: 9-22 months). The cross incision plasty is a new, safe, and efficacious technique to correct dorsal and palmar neosyndactyly and reconstruct the web space after burn injury.

We present a case of acquired syndactyly secondary to keloid formation in a previously normal web space following release of syndactyly in the adjacent web space.

The loss of web space may be congenital or acquired. Although local skin flaps are usually preferred, recurrence rate is fairly high. In this study, we used the VM-plasty as a versatile technique to create a web space and expanded its applications. Thirteen patients (7 males and 6 females) with 22 syndactylous webs were operated on using this technique. The web contractures were developed on scarred tissues in 9 patients, whereas only 4 cases presented with primary congenital syndactylies. The skin graft was not used in any of the patients. All the patients gained web functions with a good esthetic appearance without any recurrence. The technique is fairly versatile and can be used both in the hand and foot for congenital complete or incomplete syndactylies and acquired web space contractures. So, we advise the VM-plasty both in primary and recurrent cases with web space loss.

Background: The concomitant occurrence of breast cancer and pregnancy is relatively uncommon. We report the case of a patient with syndactyly, cleft hands, and absence of distal finger phalanges associated with maternal exposure to chemotherapeutic agents during the first trimester of pregnancy. These associations have not been previously described., Case: The patient was born by normal delivery after 38 weeks of pregnancy. His mother became pregnant while receiving chemotherapy (cyclophosphamide, 5-fluorouracil, and adriamycin) for breast cancer, and the fetus was exposed to these drugs from conception to the 16th week of pregnancy. At birth, anomalies were observed, including a high-arched palate, microcephaly, a flat nasal bridge, bilateral syndactyly in the first and second fingers with a hand cleft between the second and third fingers and hypoplasia of the fifth fingers, and dystrophic nail of the fourth finger of the left hand. The patient's growth and development were deficient., Conclusions: The malformations associated with in utero exposure to these chemotherapeutic agents are highly variable, but growth deficiency and anomalies of the craniofacial region and limbs are the most common. The pattern of malformations in children who were congenitally exposed to chemotherapeutic agents appears to be directly related to the age at and duration of exposure, rather than to the specific drug itself. Effective contraception is essential for the safe use of a potential teratogen in nonpregnant women of reproductive age., (Birth Defects Research (Part A), 2005. (c) 2005 Wiley-Liss, Inc.)

Introduction: Burns of the hands may result in the formation of web space contractures-post burn syndactyly. We present our experience using the three-square technique originally described by Bandoh for minor syndactyly., Method: Tissues of the contracted web are regard as forming three facets of a cube. If elevated and transposed 90 degrees on their base the facets will fall into place and line the interior of the cube creating a deepened web-space. The first flap is based on the web itself either dorsally or volarly. The second flap is based distally on one of the fingers. The third flap is based laterally on the other finger. Surgery is followed by a splinting regimen., Results: The design of the flaps is simple and the operation is easy to perform. This technique has achieved good functional and cosmetic results; there have been no flap losses or significant complications., Conclusion: The three-square-flip-flap is a simple reliable and safe method for the treatment of post burn syndactyly.

Focal Dermal Hypoplasia/Goltz Gorlin syndrome is a rare syndrome characterized by widespread dysplasia affecting tissues of mesodermal and ectodermal origin with cutaneous, osseous, ocular, oral and dental defects. Enamel hypoplasia is the most commonly reported dental manifestation and has recently been described as a possible manifestation of Lyonisation. This article reviews the reported dental findings and reports a new case with typical findings of focal dermal hypoplasia, which has been under review on our department for 10 years. It discusses the differential diagnosis as well as newer concepts of aetiology and pathogenesis in relation to dental anomalies. Enamel hypoplasia may make plaque control difficult, resulting in generalized gingivitis. Hand anomalies may limit dexterity and exacerbate this. From the dental standpoint we emphasize the implementation of timely preventive and/or therapeutic strategies. Since there are periods of exacerbation during the course of this syndrome, regular surveillance from an early age with the frequency of visits increasing during and after adolescence is indicated. The role of the dentist in improving aesthetics and function can have tremendous psychological impact to enhance self-esteem of such patients.

Background: Acquired syndactyly is a rare disease that occurs mostly after disease, trauma, or other inflammatory conditions. It is usually treated by surgical incision with a flap or full-thickness skin graft, which is very invasive and requires hospitalization., Objective: The objective was to treat acquired syndactyly with an epidermal graft by suction blister after radiosurgery, because this procedure is much less invasive and can be performed in an outpatient base., Methods: A 65-year-old Korean woman had acquired syndactyly after various traditional treatments for tinea pedis. Five days after separation of syndactyly with radiosurgery, we prepared an epidermal sheet by suction blister, placed it on sterile meshed gauze, and applied it to the separated lesion., Results: The patient's lesion was completely healed after 7 days., Conclusion: Gauze-fixed epidermal graft after radiosurgery is a very effective and simple treatment for shallow acquired syndactyly.

Background: We report a new case of oculo-dento-digital syndrome., Methods: Case report., Results: We saw a 34-year-old women with oculo-dento-digital syndrome. Visual acuity was no perception of light (RE) and 1/35 (LE). Biomicroscopy revealed a flat anterior chamber and an advanced cataract. The intraocular pressure (IOP) was 60 mmHg in both eyes. Ultrasonographic biomicroscopy demonstrated a closed chamber angle in both eyes. Measurements of the axial length and of the diameter of the lens were 18.7 mm/6.0 mm for the RE and 18.7 mm/5.8 mm for the LE respectively. In the time following we conducted a cyclodestructive procedure in the RE and a cataract extraction with implantation of an intraocular lens in the LE. This led to a considerable reduction of the IOP in the RE and combined with local therapy to IOP regulation in the LE., Conclusion: In this patient nanophthalmos, cataract and spherophakia led to angle-closure glaucoma in both eyes. We recommend early monitoring of IOP, axial length and lens diameter. This case demonstrates that an early cataract extraction might beneficially influence the natural course of the disease.

Molecular analysis of the reciprocal chromosomal translocation t(12;22)(p11.2;q13.3) cosegregating with a complex type of synpolydactyly showed involvement of an alternatively spliced exon of the fibulin-1 gene (FBLN1 located in 22q13.3) and the C12orf2 (HoJ-1) gene on the short arm of chromosome 12. Investigation of the possible functional involvement of the fibulin-1 protein (FBLN1) in the observed phenotype showed that FBLN1 is expressed in the extracellular matrix (ECM) in association with the digits in the developing limb. Furthermore, fibroblasts derived from patients with the complex type of synpolydactyly displayed alterations in the level of FBLN1-D splice variant incorporated into the ECM and secreted into the conditioned culture medium. By contrast, the expression of the FBLN1-C splice variant was not perturbed in the patient fibroblasts. Based on these findings, we propose that the t(12;22) results in haploinsufficiency of the FBLN1-D variant, which could lead to the observed limb malformations.

Sclerosteosis describes an autosomal recessive form of hyperostosis corticalis generalisata (MIM 239100). Sclerosteosis is primarily a disorder of osteoblast hyperactivity and metabolic abnormalities are not present. Besides generalized bone changes the presence of asymmetric cutaneous syndactyly of the index and middle fingers is characteristic. In many cases this syndactyly is associated with nail dysplasia and therefore dermatologists should recognize this clinical finding as a possible marker of this entity. We report on a 36-year-old female of Greek origin who had had finger and nail dysplasias and facial asymmetry since birth. The patient was hospitalized on the Neurology ward because of increasing spastic and ataxic gait disturbances. Physical examination revealed numerous neurological problems resulting from bony compression of nerves. Furthermore the patient had remarkably deformed fingers with hypoplasia of the second finger on both sides. The nails were dysplastic, especially on both index fingers. All laboratory results concerning metabolic diseases were normal. It has been shown that sclerosteosis is clinically and radiographically very similar to van Buchem disease. Through a genome-wide search with a highly polymorphic microsatellite the gene responsible for van Buchem disease has been mapped to 17q12-q21, and Balemans et al. (1999) assigned the locus for sclerosteosis to the same region providing genetic support for the hypothesis of allelism. Dermatologists should be able to interpret such syndactyly associated with nail deformities as a possible hint for the diagnosis of sclerosteosis in patients with hyperostotic features., (Copyright 2001 S. Karger AG, Basel)

Syndactyly, a failure of the digits to separate into individual units, affects about 8 to 9 per 1000 newborns and results from an aberration of the normal development of the interdigital tissues. Limb digit separation is the result of programmed cell death (apoptosis). Lysosomes play a role in the process of cell self-destruction. Our experiment was designed to test the hypothesis that the intensity of interdigital lysosomes increases during the separation of digits in vivo and in vitro. The primary mouse monoclonal antibody, 1D4B, detects the presence of lysosomes by identifying the LAMP-1 glycoprotein on the lysosome cell membrane. In our experiment this antibody immunodetected interdigital lysosome proteins in serial sections of limbs from Swiss-Webster mouse embryos, gestational ages E12.5 through E15, key developmental stages for digit separation. Digit separation was associated with an increase in intensity of lysosomal protein staining. In E12.5 limbs, the presence of lysosomes was enriched in the distal aspect of the interdigital tissue. However, the number of lysosomes markedly increased in the E13 and E14 limbs, including the entire length and width of the interdigital tissue in the E14 limbs. This lysosomal protein presence in E14 limbs was significant compared to E12.5, E13, and E15 limbs. By day 12.5, the mouse embryo limb is committed to digit separation. Addition of retinoic acid to the culture medium of limbs earlier in development, such as E12, results in induction of the process of digit separation. Cultured E12 limbs that did not receive an addition of retinoic acid, did not show digit separation. We conclude that in the limb development process, the enrichment in interdigit LAMP-1 proteins, may indicate a relationship between lysosomes, apoptosis, and digit separation. We also conclude that retinoic acid has an important role in digit separation in vivo, as shown in limb development, and demonstrated through the addition of retinoic acid to media of cultured tissues.

The term epidermolysis bullosa refers to a group of disorders characterized by skin blistering following minor trauma. The hands, because of constant use during normal daily activity, are especially exposed to blistering, with secondary scarring leading to pseudosyndactyly, adduction contracture of the thumb, and flexion or extension contracture of the fingers. The standard surgical approach for the correction of these deformities is based on the incisional release of pseudosyndactyly and contractures, and split skin grafting of the secondary wounds. A simplified approach without skin grafting is presented in this paper. Four children (8 hands) underwent 25 operations over two decades. The results, in terms of postoperative healing and recurrence, were comparable with those of the standard approach involving skin grafting.

The authors describe a new technique for division in syndactyly. The web space is reconstructed using two reverse V-Y island triangular flaps. The flaps are raised both on the dorsal and the palmar aspect of the hand. This technique does not require the use of a skin graft. Fourteen syndactylies in 9 children-three incomplete (two congenital and one secondary to burn) and six complete-were treated using this technique. The results after a maximum 4-month follow-up and the advantages of the technique are discussed.

Epidermolysis bullosa hereditaria dystrophica mutilans Hallopeau-Siemens is an autosomal recessive, chronically mutilating disease. Causal therapy is not known. In a five-year-old boy suffering from this disease and having the right hand completely clumped to a fist, syndactyly and contraction release was performed. The wounds healed under the care of the silicone-coated polyamide net dressing Mepitel. Under intensive postoperative physio- and ergotherapeutic care, a major part of his previous hand function could be restored. Complete epithelialization occurred within four weeks. Twelve months after the procedure, the area of the previous lesions was marked by an unexpected mechanical stability. It was very impressive to see the improvement in his psychological well-being and his sense of self-esteem during this period of partial recovery of his hand function.

Constriction band syndrome is a fairly common congenital hand disorder. Proposed etiologies for the formation of the anomalies are reviewed in this article and demographics for the syndrome are presented. Varied clinical presentations are addressed and potential treatment options are reviewed.

We describe the first report of distal obstructive uropathy and prune-belly syndrome in an infant with amniotic band syndrome. Prenatal ultrasonographic examination in the third trimester revealed intermittent oligohydramnios, bilateral hydronephrosis, and megacystis. Postnatally, the infant was found to have a scalp defect, a skin pedicle, pseudosyndactyly and constriction rings on the hands, marked distention of the abdomen, a fibrous band attached to the proximal urethra causing urethral stricture, a swollen penile shaft, bilateral talipes equinovarus, and syndactyly of the feet. Multiple fibrous amniotic bands could be identified in the placenta. Our case shows that fetal distal obstructive uropathy can be associated with the congenital constriction band syndrome.