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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.

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.

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.

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.

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].

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.

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.

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.

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.

Brown in 1941 reported on five families having two members with Meniere's syndrome. In 1949 she reported on three siblings (children of first cousins) and two identical twins bearing the syndrome. Bernstein in 1965 reported on seven families having two or more members afflicted by the symptoms. All these reports showed association between Meniere's syndrome and migraine headaches. None provided detailed pedigree studies in order to clarify the mode of genetic transmission. We report on a father, three daughters, and one son with typical Meniere's syndrome and paroxysmal headaches. The pedigree strongly suggests autosomal dominant transmission. After studying this family we have been paying close attention to family histories of Meniere's syndrome patients. It is not at all uncommon to hear about other members of the family with the syndrome, but it is difficult to document all of the cases for logistical reasons.

A Chinese woman presented with a spontaneous pneumothorax and a family history suggestive of the autosomal dominant transmission of pneumothorax. The patient also had skin fibrofolliculomas and folliculin gene deletion, compatible with Birt-Hogg-Dube (BHD) syndrome. The importance of BHD syndrome and other familial spontaneous pneumothoraces is discussed.

Transthyretin (TTR) amyloid neuropathy is the most severe neuropathy of adulthood with autosomal dominant transmission [1]. Liver transplantation is the only therapeutic approach available, and can...

We describe 2 unique kindreds with familial occurrence of esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) and reviewed the literature on familial EA+/-TEF. EA+/-TEF appears to be causally heterogeneous with evidence pointing to the existence of non-genetic developmental and multifactorial forms. The literature suggests that the parents of a single affected child should be given an empiric recurrent risk between ½ and 2%, rising to 20% if more than one sib is affected. The empiric risk of an affected child born to an affected parent is 3–4%. Empiric risk figures are useful in counseling families at the present time; however, the 2 kindreds presented here raise the possibility of autosomal dominant transmission in certain families. A third generation of affected offspring, or additional family reports should help to clarify this issue in the future.

Multiple trichoepithelioma is an uncommon skin disease with autosomal dominant transmission. It is characterized by multiple, benign facial skin lesions. These lesions constitute a formidable cosmetic and therapeutic problem. Treatment modalities are numerous and varied. In a few rare cases, confluence of the lesions may result in occlusion of the auditory canal, with consequent loss of hearing. In such cases the treatment of choice should be excision and split-thickness skin grafting.

A British pedigree multiply affected by the Gilles de la Tourette syndrome and spanning six generations is described. Of 122 members identified, 85 were individually interviewed, and 50 were diagnosed as ‘cases'. ‘Cases' consisted of 29 with definite or probable Gilles de la Tourette syndrome, 17 with definite or probable chronic multiple tics, and four with definite or probable obsessive-compulsive behaviour. Only eight of the 50 ‘cases' had consulted a doctor for their symptoms. ‘Cases' and ‘non-cases' could be distinguished on the basis of echo-phenomena, obsessive-compulsive features, self-injurious behaviour, and the trait score of the Leyton Obsessional Inventory, but did not differ significantly on any other psychopathological variables. The pattern of inheritance of the Gilles de la Tourette syndrome in this pedigree is consistent with autosomal dominant transmission.

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Trigeminal neuralgia (TN) is paroxysmal, lancinant pain often described as an "electric wave" by patients, with involvement of the divisions of the fifth cranial nerve. Demyelinating, compressive, ischaemic diseases are involved in the physiopathology of TN, but there are some cases without explanation. Familial TN (FTN) is a rare condition, about 1%-2% of all TN cases, while sporadic cases are the most common. To date, there have been about 126 reports of FTN. We describe the case of a 66-year-old man who had been complaining for 3 years of right-side paroxysmal lancinating pain in the second division of the fifth cranial nerve. A brain MRI with angiographic sequences did not show neurovascular conflicts or other pathological conditions. The patient had a family history of TN, which had been diagnosed in 3 other family members (father, sister and first cousin), who had undergone medical or surgical treatment for TN. There was no family history of hypertension, metabolic disorders, neurological or traumatic diseases. Animal studies have shown a probable involvement of genes codifying for calcium channels as the starting alterations in trigeminal excitability. Our FTN could be a good model to investigate the role of gene mutations in this condition.

Introduction Neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a frequent genetic disease with autosomal dominant transmission representing 95% of all phacomatosis. There have been numerous reports published about the physical aspects of neurofibromatosis, while psychological issues have been given little attention so far. Objectives The aim of our case report is to highlight the possible association of NF1 and psychotic symptoms, to underline the usefulness of a complete somatic examination when confronting with epileptic or mentally retarded teens experiencing an hallucinatory syndrome. Case report We report the case of a 17-years-old boy, with consanguineous parents and history of mental retardation and generalized epilepsy since the age of three, consulting for auditive and visual hallucinations and an heteroagressiveness since two months. Skin examination found signs of NF1. Electroencephalography (EEG) showed no epileptic abnormalities and brain MRI showed no abnormalities than could explain the psychotic symptoms that are usually parts of the organic brain syndrome. A medication by 2 mg per day of Risperidone has completely eliminate the psychotic symptoms within two months and is continued for one year at least. Conclusion Neurological and psychiatric disorders are often intricate. Psychiatrists should have a better knowledge of both psychiatric and somatic manifestations of NF1 to not pass through the right diagnosis and to ensure to these patients better intellectual, academic and social skills.

Supernumerary teeth are common in the general population and occur more frequently in-patients with family history of such teeth. Multiple supernumerary teeth are associated with cleidocranial dyplasia and Gardner syndrome. However it is rare to find multiple supernumeraries in individuals with no other associated disease or syndrome. We describe the occurrence of multiple supernumerary teeth in a family occurring as a non-syndromal trait. The autosomal dominant transmission of non-syndromal multiple supernumerary teeth is new.

Pachydermoperiostosis (idiopathic or primary hypertrophic osteoarthropathy) is a rare condition of unknown origin involving the skin and the skeleton, with an autosomal dominant transmission. We report a case of anaemia in a patient with pachydermoperiostosis indicating myelofibrosis, and review the literature and the pathogenetic mechanisms.

The paroxysmal facial pain of trigeminal neuralgia is usually idiopathic, but familial cases have been described. We describe a family with apparent autosomal dominant transmission of trigeminal neuralgia. Our cases and a review of the literature suggest that the etiology of trigeminal neuralgia may be vascular compression of the fifth cranial nerve. Autosomal dominant vascular and epileptic disorders are reviewed, and possible relationships to familial trigeminal neuralgia are considered.

Congenital hypoplastic anemia (CHA) or Blackfan-Diamond anemia (BDA) is a rare congenital abnormality of erythropoiesis characterized by normochromic, macrocytic anemia presenting in infancy or early childhood. Associated phenotypic abnormalities such as triphalangeal thumbs and cleft lip and/or palate are found in 70% of cases. Although most cases are sporadic, several reports suggest either autosomal dominant or autosomal recessive inheritance. We report on a 3 generation family with autosomal dominant inheritance of CHA. © 1994 Wiley-Liss, Inc.

We report a family with nine subjects over three generations affected with an omphalocele requiring surgical intervention within the first few days of life. Because of the vertical transmission and male to male inheritance in our family, we conclude that an autosomal dominant gene caused the omphalocele in the affected family members. The paternal great grandfather of the proband was not clinically affected but produced two children with omphaloceles with different spouses.

Cerebro-costo-mandibular syndrome is a rare disorder characterized by rib malformations, various degrees of cerebral maldevelopment, mental deficiency, palatal defects, and micrognatia. This syndrome was first described in 1966. The majority of cases are sporadic, but a few instances of familial occurrence have been reported, some with an autosomal recessive pattern of inheritance. Mortality in early age has been high, probably mostly due to respiratory insufficiency secondary to rib abnormalities and flail chest. We report a mother and son with this disorder, suggesting autosomal dominant transmission.

1report on the autosomal dominant transmission of malignant mesothelioma in two villages of Cappadocia (Turkey), irrespective of the length of exposure to erionite. Malignant mesothelioma is a sporadic malignant disorder linked to exposure to asbestos. Since the 1970s, the question of possible genetic susceptibility with an autosomal dominant inheritance pattern has been raised in several reports of familial cases. 2

Spondylometaphyseal dysplasia was first described by Kozlowski et al. in 1967 as a new dysplastic bone disease, characterized by metaphyseal dysplasia associated with generalized platyspondyly in the vertebral column [1]. Kozlowski ct ai. have pointed out the autosomal dominant transmission of this disorder at that time. However, later reports showed that thc manner of genetic transmission and the degree of the manifestation of the radiological findings could be variable and accordingly seven types of spondylometaphyseal dysplasia were described [2]. In this article, three cases displaying one of the rare forms of spondylometaphyseal dysplasia,"type VII" Lire presented and the diagnostic findings as well as the differential diagnostic criteria are discussed.

This case reports 4-year-old monozygotic twins incompletely concordant for simple congenital ptosis. Pedigree analysis demonstrates 4 generations of autosomal dominant transmission. The case and pedigree are reviewed in light of a number of recent advances in the understanding of genetic influences on simple congenital ptosis.

Hereditary hypotrichosis simplex of the scalp is a genotrichosis characterized by a hair defect limited to the scalp in the absence of other ectodermal or systemic abnormalities. Only large pedigrees consistent with autosomal dominant transmission have been described to date. In this article the clinical and scanning electron microscopy findings of a nonfamilial case of congenital scalp hypotrichosis simplex are reported. In some patients the diagnosis of sporadic hypotrichosis simplex of the scalp should be considered after ruling out all other possible causes of congenital and hereditary hypotrichosis.

Hereditary motor-sensory neuropathy type III (HMSN III) (Dejerine-Sottas disease) is a severe demyelinating neuropathy that is traditionally considered autosomal recessive. We report a father and daughter diagnosed with HMSN III by clinical, electrophysiologic, and pathologic criteria, thus showing that it may be transmitted in an autosomal dominant fashion in selected families.

Familial thrombocytosis is an extremely rare disorder, so far reported in only a handful of families. In the majority of cases the characteristics were of essential thrombocythemia. Most patients presented with a platelet count above 800 000/mm 3 , were diagnosed as having a myeloproliferative disease, and some required chemotherapy. We describe a benign form of familial thrombocytosis with autosomal dominant inheritance in five healthy members of three generations of a family, all of whom had moderate thrombocytosis within the range 422 000-662 000/mm 3 , characterized by low mean platelet volume. A careful medical history and a 5-year follow up of the subjects did not reveal any untoward clinical development. This variant of familial thrombocytosis is therefore of a benign nature. Possible mechanisms linking thrombocytosis with platelet microcytosis in this family are discussed.

We studied 47 subjects belonging to 13 unrelated families with a history of mild haemorrhagic diathesis and chronic thrombocytopenia. 36 patients presented some degree of thrombocytopenia: 7/36 (19%) had slight thrombocytopenia (100-150 x 10(9)/L); 26/36 (72%) had mild thrombocytopenia (50-100 x 10(9)/L) and 3/36 (8%) had severe thrombocytopenia (< 50 x 10(9)/L). No correlation was observed between platelet count and the degree of haemorrhagic diathesis, which was mild in the majority of patients. Transmission was autosomal dominant. Platelet anisocytosis, increased percentage of large platelets and absence of leukocyte inclusions were observed in 26/30 (87%) of the examined blood smears. The ultrastructural appearance of platelets was normal. Megakaryocytes appeared normal in number in 10/10 patients, but showed asynchronous nuclear-cytoplasm maturation and mainly nonlobulated nuclei. Platelet aggregation was studied in 26 patients and either increased or decreased curves were variably observed in response to different aggregating agents. Platelet-associated IgG (PAIgG) was increased in 18/31 (58%) patients, while serum autoantibodies against platelet glycoproteins Ib/IX or IIb/IIIa were demonstrable in only 1 case. An increased expression of platelet surface glycoproteins Ib and IIb/IIIa, as studied by murine monoclonal antibodies binding in 17 cases, was observed. Platelet survival performed by 111Inoxine-labelled autologous platelets was normal in the 3 studied patients. Congenital macrothrombocytopenia confirms to be a distinct clinical disorder for which the name of "chronic isolated hereditary macrothrombocytopenia" is proposed.

Dehydrated hereditary stomatocytosis (DHS), also known as ‘hereditary xerocytosis’, is a rare form of hereditary haemolytic anaemia with autosomal dominant transmission. This genetic disorder is pr...

The Currarino triad is a hereditary transmitted syndrome, originally defined by Currarino as ASP-association, consisting of an anorectal malformation, a sacral bony defect and a presacral mass. In most cases autosomal dominant transmission is suggested. In family members one or two features of the syndrome may be missing, indicating an incomplete form of this complex. We describe two unrelated girls at the age of 8 and 9 months respectively with ASP-association. Family screening in both patients showed 8 additional cases with a complete or incomplete Currarino triad, four of them being asymptomatic. A review of the literature up to 1991 revealed 48 patients with ASP-association. In more than 80% of cases, this complex is diagnosed in the first decade, whereas incomplete Currarino syndrome is diagnosed predominantly in adults. Most frequently the presacral mass in ASP-association was reported to be an anterior meningocele (47%) and a benign teratoma (40%). The number of patients with Currarino syndrome has been underestimated so far. We recommend anorectal examination, pelvic ultrasound and pelvic x-rays in all patients with a history of chronic constipation since early childhood. Positive findings should lead to further investigations such as barium enema, MRI, myelography and family screening. Close cooperation between pediatric surgeons and neurosurgeons is required to ensure adequate surgical treatment, considering both the risk of malignant degeneration as well as the risk of intraoperative nerve damage. Thus, radical excisional surgery is not obligatory in every case of Currarino syndrome.