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The incidence of Osler–Weber–Rendu disease is low, ranging from 1 detected case per 50,000 to 1 per 100,000 population. The disease is hereditary, with autosomal dominant transmission, caused by pathogenic mutations in genes involved in angiogenesis. The disease has a pronounced clinical picture of multiple telangiectasias of the skin and mucous membranes and manifests as spontaneous bleeding. This scientific article presents a clinical analysis of a 65-year-old patient with a diagnosis of Osler–Weber–Rendu disease. Early identification of the manifestations of this disease and careful observation of the patient give a favorable prognosis of the course and prevent the development of severe complications.

Reportamos el caso de lactante con colestasis que fue diagnosticado como síndrome de Alagille sindrómico. La característica principal de la enfermedad es la escasez de conductos biliares. Es una enfermedad hereditaria, de transmisión autosómica dominante con penetración incompleta, secundaria a mutaciones en los genes JAG1 (más del 90%) y NOTCH21, que inducen una alteración del desarrollo embriológico que afecta a estructuras dependientes del mesodermo1.Describimos el caso y discutimos sus hallazgos clínicos y radiológicos.

Branchial arch anomalies can arise from the four first branchial arches, but the most encountered cases are from the second one. Second branchial arch cysts and abscesses occur mainly in older children or young adults while fistulae are discovered in young children. We report a case of complete second branchial arch fistula of Bailey III type with adult complaints of painful swelling and local reddishness followed by spontaneous discharge and disappearance of complaints. Diagnosis was based on ultrasound and confirmed by CT scan, with the classic “beak sign” visible on both exams. Three cases were encountered in the family, with no otologic or kidney symptoms, which is quite different from the classical branchiootorenal syndrome which associates severe inner ear and kidney congenital anomalies.

International audience; Purpose : Heritable thoracic aortic aneurysms and dissections (hTAAD) are life-threatening complications of well-known syndromic diseases or underdiagnosed nonsyndromic heritable forms (nshTAAD). Both have an autosomal dominant transmission and are genetically heterogeneous. Our objective was to describe the relevance of molecular diagnosis in these patients and the contribution of each gene in nshTAAD. Methods : Two hundred twenty-six consecutive nshTAAD probands, either young (

Reactive perforating collagenosis (RPC) is a rare form of dermatosis. It forms with perforating folliculitis, Kyrle's disease, and serpiginous perforating elastosis, which is a group of perforating dermatosis. RPC can be hereditary with autosomal dominant transmission or it can be acquired, which is usually observed in diabetics with chronic renal failure. Here we report a new observation in a 72-year-old woman treated by phototherapy with a favorable outcome.

Neurofibromatosis type 1 is a multisystem genetic disease of autosomal dominant transmission that reveals important cutaneous manifestations such as café-au-lait spots, multiple neurofibromas, and ephelides in skin fold areas, as well as hamartomatous lesions in the eyes, bones, glands, and central nervous system. Moyamoya disease is a rare progressive vaso-occlusive disorder that occurs with important ischemic cerebrovascular events. Despite the rarity of this association in childhood, children diagnosed with neurofibromatosis type 1 and focal neurologic symptoms should be investigated for moyamoya syndrome. The present study reports the case of a pediatric patient with a rapidly progressive cerebrovascular accident and a late diagnosis of Neurofibromatosis type 1 associated with moyamoya disease.

Cleidocranial dysplasia (CCD) is a rare syndrome with an estimated prevalence of 1:1 000 000.[1 2][1] It has an autosomal dominant transmission with complete penetrance and variable expression, equally affecting men and women.[3][2] This skeletal disorder is caused by a mutation in the RUNX2 (CBFA1

espanolEl Complejo Esclerosis Tuberosa (CET) es una enfermedad de origen genetico, multisistemica de transmision autosomica dominante, se debe a la mutacion de los genes TSC1 (Tuberose Sclerosis Complex 1) y TSC2 de los cromosomas 9 y 16 respectivamente. Las manifestaciones clinicas se deben a la presencia de lesiones tumorales benignas (harmatomas) en diferentes organos lo que genera un amplio espectro de signos y sintomas. El caso que se presenta es de una adolescente de origen aymara con epilepsia, retraso mental y lesiones dermicas tipicas. Es una enfermedad poco frecuente en nuestro medio y rara en personas de origen indigena, no encontrandose ninguna descripcion en la literatura nacional. Por la multiplicidad de las manifestaciones clinicas, se hace necesario divulgar la informacion para que que las diferentes especialidades medicas reconozcan y diagnostiquen esta patologia tempranamente para un tratamiento adecuado, oportuno y interdisciplinar. EnglishThe Tuberose Sclerosis Complex (TSC) is a genetic, multisystemic disease of autosomal dominant transmission, due to the mutation of the TSC1 and TSC2 genes of chromosomes 9 and 16 respectively. The clinical manifestations are due to the presence of benign tumor lesions (harmatomas) in different organs, which generates a wide spectrum of signs and symptoms. The case presented is that of a teenager of Aymara origin with epilepsy, mental retardation and typical skin lesions. It is a rare disease in our environment and rare in people of indigenous origin, no description found in the national literature. Due to the multiplicity of the clinical manifestations, it is necessary to disseminate the information so that the different medical specialties recognize and diagnose this pathology early for an adequate, timely and interdisciplinary treatment.

Hidradenitis suppurativa is a chronic skin disease characterised by repeated skin abscesses with sinus tracts and scar formation. Currently, the aetiology and pathogenesis of hidradenitis suppurativa remain unclear. Genetic factors, immune disorders, hormonal abnormalities, skin-microbial dysbiosis, smoking, obesity and mechanical friction all influence hidradenitis suppurativa pathogenesis. Moreover, hidradenitis suppurativa has a familial subset with autosomal dominant transmission proposed and is related to a mutation of γ-secretase component genes. In this review, we analyse and summarise research progress regarding the relationship between the γ-secretase gene dysfunction and the pathogenesis of hidradenitis suppurativa.

Familial hypercholesterolemia (FH) is a genetic disease with autosomal dominant transmission, characterised by high blood cholesterol levels. The evolution of this disease leads to primary atherosclerosis and cardiovascular disease. Patients with HF develop atherosclerosis by the age of 20 and usually do not survive past the age of 30. We present the case and oro-dental aspects of a preschooler that was diagnosed at the age of 4 with FH, compound heterozygote (mutation/genotype1 LDLR: C20IX, exon 4; mutation/genotype2 LDLR: G571E, exon 12) and the experience of our clinic in the management of this patient that received off-label treatment with statins. When diagnosed, his cholesterol level was 932 mg/dL and his LDL-cholesterol level was 792 mg/dL. Treatment with rosuvastatin and ezetimibe was prescribed. Both substances (rosuvastatin and ezetimibe) are not approved for children under the age of 6 in Europe. Taking into considerations the diagnosis and prognosis for unfavorable evolution, treatment with statins was started at the age of 5 years.

Introdução:O linfedema primário consiste num edema crónico dos tecidos, mais comumente presente nos membros inferiores. Caso:Lactente de um mês do sexo masculino, previamente saudável, observado por edema firme da perna e pé esquerdos e hidrocelo bilateral recente. Sem sinal de godet, outros sinais inflamatórios ou limitação articular. Apresentava sobreposição dos dedos e alterações tróficas das unhas dos pés. Aos cinco meses surge edema semelhante no pé direito. Bisavó com edema bilateral dos membros inferiores desde a infância. Apresentação consistente com Doença de Milroy. Posteriormente, necessidade de internamentos por celulite. Eco-doppler dos membros inferiores sem alterações vasculares. Estudo do gene FLT4 negativo. Iniciada drenagem linfática com franca melhoria. Atualmente, clinicamente estável. Comentários/Discussão: Doença rara, caracterizada por anaplasia/hipoplasia dos vasos linfáticos e edema dos membros inferiores, geralmente bilateral, podendo cursar com hidrocelo, celulite recorrente e alterações nas unhas. Transmissão autossómica dominante, mas mutação encontrada em apenas 70% dos indivíduos afetados.vv, NASCER E CRESCER - BIRTH AND GROWTH MEDICAL JOURNAL, Vol 26, No 1 (2017)

Holt-Oram syndrome, also known as hand-heart syndrome, is classically described to have upper limb anomalies affecting the thumb and heart, mostly septal defects. The syndrome may occur sporadically but commonly follows autosomal dominant transmission. Most cases are caused by a mutation in the transcription factor gene TBX5, located on 12q24.1. Holt-Oram has 100% penetrance and variable expressivity. If the disorder is suspected prenatally, thorough evaluation of the fetal heart is warranted because more than 75% of fetuses are affected with congenital heart disease. Similarly, due to the upper extremity involvement, the fetal radius-ulna-hand complex needs to be evaluated. A multidisciplinary approach is imperative, including a geneticist, hand surgeon, pediatric cardiologist, and maternal-fetal medicine subspecialist.

Van der Woude syndrome (VWS) is an autosomal dominant malformation syndrome characterized by orofacial clefting (OFC) and lower lip pits. The clinical presentation of VWS is variable and can present as an isolated OFC, making it difficult to distinguish VWS cases from individuals with non-syndromic OFCs. About 70% of causal VWS mutations occur in IRF6, a gene that is also associated with non-syndromic OFCs. Screening for IRF6 mutations in apparently non-syndromic cases has been performed in several modestly sized cohorts with mixed results. In this study, we screened 1521 trios with presumed non-syndromic OFCs to determine the frequency of causal IRF6 mutations. We identified seven likely causal IRF6 mutations, although a posteriori review identified two misdiagnosed VWS families based on the presence of lip pits. We found no evidence for association between rare IRF6 polymorphisms and non-syndromic OFCs. We combined our results with other similar studies (totaling 2472 families) and conclude that causal IRF6 mutations are found in 0.24-0.44% of apparently non-syndromic OFC families. We suggest that clinical mutation screening for IRF6 be considered for certain family patterns such as families with mixed types of OFCs and/or autosomal dominant transmission.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder that affects over one in 500 persons worldwide. The autosomal dominant transmission of HCM implies that many relatives are at risk for HCM associated morbidity and mortality, therefore genetic testing and counselling is of great importance. However, in only 50-60% of the patients a mutation is found, which hampers predictive genetic testing in relatives. In HCM patients in whom the causal mutation has not been identified (yet), phenocopies of HCM - i.e. diseases that mimic HCM - could be responsible for the HCM phenotype. One of the HCM phenocopies is transthyretin amyloidosis (ATTR), caused by mutations in the transthyretin (TTR) gene. From 697 HCM index patients referred to our cardiogenetics outpatient clinic and tested for HCM associated genes between January 1997 and December 2012, we selected the ones without a detected causal mutation (n = 345). In these patients, additional DNA analysis of the TTR gene was performed. In four patients (1.2%), a TTR mutation was detected (E7G, V30M, T119M, V122I). The E7G mutation is probably a non-pathogenic mutation. The T119M mutation is a known TTR mutation, but does not cause a cardiac phenotype. So in two (0.6%) patients, TTR analysis identified the cause of their HCM. ATTR should always be considered in patients with unexplained HCM, especially because of the great benefit of an early diagnosis regarding treatment and prognosis

Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias. The syndrome is characterized by a typical electrocardiographic pattern in the right precordial leads. This article will focus on the new electrocardiographic features recently agreed on by expert consensus helping to identify this infequent electrocardiographic pattern.

We report a 45-year-old Japanese man with SCA19/22. Whole-exome sequencing revealed a heterozygous missense mutation (c.1169G>A, p.S390N) in the KCND3 gene. Although this mutation has been reported to cause SCA19 in a Dutch patient, a co-segregation study of the mutation has not been carried out. In the present family, since the S390M mutation was found in the patient but not in the unaffected siblings, we suspected co-segregation of this mutation with the disease in our family. Our patient presented with juvenile-onset pure cerebellar ataxia associated with pes cavus, which has not been previously described in SCA19/22. Thus, our patient would expand the clinical spectrum of SCA19/22. In the case of juvenile-onset pure cerebellar ataxia with autosomal dominant transmission, SCA19/22 should be considered.

Photosensitive epilepsy (PSE) is the most common form of human reflex epilepsy, affecting up to 10 % of children with epilepsy. Moreover, between 4 and 9 % of the population carries this risk factor, and may be unaware of this risk until an unfortunate stimulus might discover it [1].

Congenital cataract is a type of cataract that presents at birth or during early childhood, and it is one of the most easily treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of 1-6 cases per 10,000 live births. Approximately 50% of all congenital cataract cases may have a genetic cause, and such cases are quite heterogeneous. Although congenital nuclear cataract can be caused by multiple factors, genetic mutation remains the most common cause. All three types of Mendelian inheritance have been reported for cataract; however, autosomal dominant transmission seems to be the most frequent. The transparency and high refractive index of the lens are achieved by the precise architecture of fiber cells and homeostasis of the lens proteins in terms of their concentrations, stabilities, and supramolecular organization. Research on hereditary congenital cataract has led to the identification of several classes of candidate genes that encode proteins such crystallins, lens-specific connexins, aquaporin, cytoskeletal structural proteins, and developmental regulators. In this review, we highlight the identified genetic mutations that account for congenital nuclear cataract.

Trichilemmal cysts (TCs) can occur as sporadic lesions or in hereditary-familial settings with autosomal dominant transmission. These entities have not been widely analyzed in their peculiar aspects yet. The aim of this study was to describe a cohort of patients with diagnosis of TCs through a clinical and biomolecular characterization, intended to highlight some effective diagnostic criteria for their identification. Among 149 cases of this study, 24 cases of TCs (16.1%) arose in patients with at least one first-degree relative with diagnosis of TCs. Peculiar findings concerning hereditary lesions included the multiple presentation with an early onset age. On the basis of clinical evaluation, we propose a panel of clinical and histologic criteria for the diagnosis of hereditary TCs, which includes: (i) the diagnosis of TCs in at least two first-degree relatives or in three first- or second-degree relatives in two consecutive generations; (ii) at least one of the patients with TCs diagnosed 5-cm lesions) or rare histopathologic features (proliferating and ossifying) TCs.

In congenital erythroid hypoplasia (Diamond-Blackfan syndrome) a genetic transmission has been described in only a few cases. We report a family where the evidence points to an autosomal dominant mode of inheritance, the first report of this kind where the father has had documented anaemia in infancy. The literature is reviewed.

A family is described in which a form of myeloproliferative disease involving the megakaryocytic cell line occurs in three generations, resulting in thrombocytosis in several members. An autosomal dominant transmission with variable penetrance is proposed, based on the distribution of involved members in the pedigree. Two family members appeared to have an abnormal chromosome 7, which is frequently observed in patients with hematological disorders. It is our opinion that the chromosomal aberration is primarily related to the mutagenicity of the cytostatic treatment, although a primary defect cannot be fully excluded.

Periventricular nodular heterotopia is a common malformation of cortical development in which the migration of developing neurons destined for the cerebral cortex is abbreviated. Bilateral periventricular nodular heterotopia is most commonly an X-linked disorder that involves mutations in the filamin A (FLNA) gene, but an autosomal recessive form and sporadic forms have been identified. To our knowledge, autosomal dominant transmission of isolated periventricular nodular heterotopia has not been reported. Periventricular nodular heterotopia has a heterogeneous phenotype, associated commonly with seizure disorder, and more recently with reading deficits and visual-spatial deficits in some patients. We present a father and son with bilateral periventricular nodular heterotopia and similar visual–spatial learning deficits, consistent with nonverbal learning disability.

Summary. The von Willebrand factor antigen (factor VIII-related antigen, VIIIR:Ag) multimer pattern has been analysed by SDS-agarose electrophoresis of plasmas from 116 patients (47 families) with von Willebrand's disease. In addition to previously recognized patterns, a subclassification was established between plasmas that had a type Ia pattern (VIIIR:Ag multimer pattern like that of normal plasma) and those that had a type Ib pattern in which there was a relative reduction in the concentration of the larger VIIIR:Ag multimers even though all multimeric forms were present. The different patterns were consistent within families and were inherited by autosomal dominant transmission. Von Willebrand's disease heterogeneity was apparent in the distribution of these plasmas: type Ia, 43 patients in 18 families; type Ib, 39 patients in 15 families; type II, 22 patients in 10 families, one of which was further classified as type IIB, one of which was type IIC, and three were IIA. Seven patients with severe von Willebrand's disease were also studied. In general, the interpretation of SDS-agarose multimer patterns corresponded to those previously obtained by crossed immunoelectrophoresis, but the former technique was more sensitive and could identify differences that were not apparent by crossed immunoelectrophoresis.

Four kindreds with family-specific malposition of cuspids were studied. Besides malposition of cuspids, the members also showed varying combinations of other anomalies: malposition, malformation or hypodontia of upper lateral incisors, second bicuspids and lower central incisors. The pedigrees provided convincing evidence for autosomal dominant transmission of the abnormalities studied. Their nature and location allow the assumption that they represent different expressions of one dominant gene causing a primary disturbance in the critical marginal area of the embryonic dental lamina.

This report gives a description of a three-generation family in which spondylocostal dysostosis associated with previously unreported neurological complaints occurred in five family members, suggesting autosomal dominant inheritance. A review of the literature is presented and previously unreported neurological complaints, e.g. neurogenic claudicatio, are emphasized.

Trigeminal neuralgia in its classic form is usually an isolated disease that occurs in sporadic fashion, but familial cases have been described. We report the case of a 45-year-old man who presented with left V2 trigeminal neuralgia. The neurological examination was normal and imaging and laboratory investigations were non-contributive to the etiological work-up. Carbamazepine gave excellent symptomatic relief. During patient evaluation, we became aware of a clustering of trigeminal neuralgia in four other family members over three generations. Familial trigeminal neuralgia has been expounded on in fewer than 30 reports in the literature. Our cases and the literature review suggest an autosomal dominant transmission. The clinical features of familial trigeminal neuralgia are described and pathophysiological implications of this genetic clustering discussed.

Herediter hemorajik telenjiektazi, otozomal dominant geçişli, birçok klinik bulguyla karakterize, anormal vasküler formasyonla ilişkili nadir gözlenen bir hastalıktır. Biz bu vakada, gastrointestinal sistemin multiple bölgesinde (özofagus, mide korpus ve antrumu, duodenum) anjiodisplazik lezyonlarla seyreden, öyküsünde dört kez geçirilmiş miyokard infarktüsü bulunan, acil servise melena ile başvuran 65 yaşındaki olguya tanı anında yapılan argon plazma koagülasyon ve supportif yaklaşım kombinasyonun tedavi başarısını gözlemledik. Tanı anında uygulanan argon plazma koagülasyon ve bipolar koagülasyon yöntemleri bir çok çalışmada tercih edilen yöntemler olmuştur. Bu nedenle biz bu olgumuzda argon plazma koagülasyon yöntemini ve çalış-malarda etkisi kanıtlanmış konservatif tedavi kombinasyonunu tercih ettik. Bizim vakamızın argon plazma koagülasyon yöntemiyle beraber destek tedavisine verdiği hızlı cevap argon plazma koagülasyonun herediter hemorajik telenjiektaziye bağlı anjiodisplazik lezyonlarda seçkin tedavi yöntemi olduğu görüşünü desteklemektedir., Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome), a vascular disorder with autosomal dominant transmission, has a variety of clinical manifestations. In this case, we monitored a 65-year-old female who admitted to our hospital with gastrointestinal bleeding. Her history revealed repeated myocardial infarction (4 times). We diagnosed multiple angiodysplastic lesions with endoscopic examination. We evaluated the success of combination treatment with argon plasma coagulation and supportive approach at the time of diagnosis. argon plasma coagulation and bipolar coagulation methods have been reported as the preferred treatments in several studies. Therefore, we preferred the combination of argon plasma coagulation and conservative treatment methods in our case. The rapid healing observed with this treatment supports that combination treatment is effective in angiodysplastic lesions associated with hereditary hemorrhagic telangiectasia

Cavernous angiomas are cerebral cavernous malformations and they are relatively rare lesions. Two forms of cavernous angiomas have been described: a sporadic form, in which patients usually have a single lesion, and a familial form, the hallmarks of which are multiple lesions and autosomal dominant transmission. The familial form appears to be very uncommon and has mainly been described in the Hispanic population. We report two cases of multiple intracranial cavernous angiomas which is an autosomal dominant pattern of inheritance. It is very rare to find this in non Hispanic population.

Introduction: Hereditary multiple exostoses (HME) or osteochondromatosis is a rare autosomal dominant disease characterized by multiple osteochondromas and skeletal deformities. Patient Concerns & Diagnoses: We present the case of a 5 years and 9 month-old patient who presented with inferior limb pain for approximately 6 months, associating also deformity of the right index finger for a month. Hand X-ray revealed a radiologic abnormality of the right radius, therefore the child was referred to our clinic for further investigations. The X-rays revealed multiple osteochondromas of the radius, metacarpal bones, hand phalangeal bones, femur, tibia, fibula, metatarsal bones, and foot phalangeal bones. We mention that the same radiological aspect was identified in the case of the patient's mother, undiagnosed until that moment. Outcomes: The particularity of this case consists in identification of a rare genetic pathology, HME in a 5-year-old patient, without any known familial history, after the occurrence of a nontraumatic joint dislocation of the right index finger. Conclusion: HME is a rare genetic condition, without a curative treatment, burdened by multiple complications, and whose diagnosis is usually established during childhood.

The few epidemiological studies conducted to date on the heterogeneous group of hereditary spastic paraplegias (HSPs) indicate a prevalence of 1.27-12.1 per 100,000. This study aims to explore the epidemiological, clinical, and genetic variability of HSPs among Sardinians, a population of peculiar ethnicity.A population-based prevalence study was performed in north-western Sardinia between January 2000 and December 2010. Multiple sources were used for case ascertainment. Familial and sporadic cases were diagnosed according to generally accepted criteria, and clinical diagnoses were validated by expert neurological examination. Clinical data and pedigree information were recorded and blood samples drawn for genetic testing.Sixty-seven HSP patients were included in the study: 59 belonged to 11 families with autosomal dominant transmission (AD-HSP), three cases were from two unrelated autosomal recessive families, and the remaining five cases were apparently sporadic. On 31 December 2010, the total crude prevalence was 19.9 per 100,000 (95 % CI 18.4-21.4), while the crude prevalence of AD-HSP was 17.5 (24.4 M, 15.7 F; M:F ratio 1.55). The mean age at examination was 48.4 years, and the mean age at onset of HSP was 36.6 years. A molecular diagnosis was obtained in 82.1 % of the cases (52 cases with mutations in SPAST/SPG4, two in SPG7, and one in SPG11).The prevalence of HSP among Sardinians is high compared with other Western European populations. The multiple search strategy used in this study and the specific socio-demographic characteristics of Sardinians may account for this finding.

We describe a three generation family in whom multiple individuals are variably affected due to a PHOX2B non-polyalanine repeat mutation. This family demonstrates extreme phenotypic variability and autosomal dominant transmission over three generations not previously reported in the wider literature. Novel findings also inclue a history of recurrent second trimester miscarriage. Pediatr Pulmonol. 2014; 49:E140-E143. © 2014 Wiley Periodicals, Inc.

Purpose: A family spanning three generations with a history of familial carotid body tumors (CBTs) was studied, and previously proposed hypotheses of tumor characteristics and genetic mode of transmission were addressed. Methods: Clinically occult lesions in adult subjects were detected by means of high-resolution computed tomography. Results: A 60% incidence of bilaterality of CBTs associated with multiple paragangliomas was noted in the family studied. The genetic mode for CBTs in this family was not simple autosomal dominant transmission and appeared to be paternally directed with complete penetrance. Conclusion: In patients with familial CBTs, high-resolution computed tomography is recommended for early screening as a means of prompting diagnosis and definitive treatment, an approach that minimizes morbidity and facilitates surgical excision. (J Vasc Surg 1999;29:649-53.)

A novel phenotype in a 3-generation family with early-onset aponeurotic ptosis and corneal limbal vascularization is described. Karyotype analysis was normal in the proband, and autosomal dominant transmission is demonstrated.

Camptodactyly is a condition characterized by a nontraumatic, fixed flexion contracture at the proximal interphalangeal joint, typically involving the fifth finger. Most occurrences are sporadic, but autosomal dominant transmission and syndromic associations have been described in the literature. We describe the case of an adolescent boy who presented to our clinic with a 2-year history of bilateral, nonsyndromic camptodactyly and knuckle pads.