Absence Of Family History Research Articles

Tremor associated with Klinefelter syndrome – A case series and review of the literature

BackgroundPrevious case series suggested a link between Klinefelter syndrome (KS) and essential tremor (ET) or an ET-like syndrome. MethodsWe investigated three KS-patients with tremor including tremor-analyzes and discuss our data in context to findings from a literature review. The clinical outcome after deep brain stimulation (DBS) is also reviewed. ResultsTremor in KS is predominantly a postural and kinetic tremor that resembles ET. Our patients were further characterized by absent family history for tremor in first degree relatives, lack of subjective alcohol responsiveness inquired by history, and tremor onset in childhood. One of our patients and two cases from literature improved after DBS of the ventral intermediate nucleus (VIM) of the thalamus. ConclusionsTremor in KS shares several features with ET. If other characteristics such as family history, alcohol responsiveness, and age at tremor onset may serve as discriminating factors from ET, needs to be further investigated. First observations suggest that VIM-DBS may be efficacious.

Discovery of a Large Deletion of KAL1 in 2 Deaf Brothers

Kallmann syndrome (KS) usually combines an anosmia and a hypogonadotrophic hypogonadism. Hearing impairment was described in a few cases of KS. Our objective is to describe an unusual presentation of KS in 2 cases and to explore the pattern of inheritance in this family. Two brothers presented with a sensorineural hearing impairment associated with cryptorchidism and abnormal movements. Genome-wide array analysis identified a large deletion of KAL1 in both patients confirming the diagnosis of Kallmann syndrome. The absence of familial history has been explained by a somatic mosaicism identified in their mother. The description of a hearing defect in 2 brothers with Kallmann syndrome allows asserting that deafness is part of the clinical features of this disease and must lead the physician to monitor the hearing function of Kallmann patients.

A sporadic case of late-onset familial amyloid polyneuropathy with a monoclonal gammopathy

A 77-year-old Portuguese woman reported gradual worsening of burning and numbness in the feet and hands, fatigue, anorexia, weight loss, diarrhoea and decreased visual acuity. She had a medical history of atrial fibrillation and recent episodes of dizziness and blood pressure fluctuations. There was no relevant family history. The diagnostic workup documented a severe axonal sensorimotor peripheral neuropathy, a monoclonal IgG kappa protein on serum, a severe left ventricular hypertrophy on the echocardiogram and probable vitreous deposits of amyloid on ophthalmologic examination. Pain and dysautonomia with an axonal neuropathy and multisystemic involvement raised the possibility of amyloidosis. The presence of a detectable monoclonal protein, older age at disease onset and absence of family history of disease usually suggest immunoglobulin light-chain amyloidosis. However, in this case, both the genetic testing and the biopsy of the salivary glands confirmed transthyretin amyloidosis. In those patients with a monoclonal protein, particularly in sporadic and late-onset cases, the diagnosis of transthyretin amyloidosis can be challenging, mimicking immunoglobulin light-chain amyloidosis.

Tremor associated with Klinefelter syndrome —/INS; A case series and review of the literature

Background: Previous case series suggested a link between Klinefelter syndrome (KS) and essential tremor (ET) or an ET-like syndrome. Methods: We investigated three KS-patients with tremor including tremor-analyzes and discuss our data in context to findings from a literature review. The clinical outcome after deep brain stimulation (DBS) is also reviewed. Results: Tremor in KS is predominantly a postural and kinetic tremor that resembles ET. Our patients were further characterized by absent family history for tremor in first degree relatives, lack of subjective alcohol responsiveness inquired by history, and tremor onset in childhood. One of our patients and two cases from literature improved after DBS of the ventral intermediate nucleus (VIM) of the thalamus. Conclusions: Tremor in KS shares several features with ET. If other characteristics such as family history, alcohol responsiveness, and age at tremor onset may serve as discriminating factors from ET, needs to be further investigated. First observations suggest that VIM-DBS may be efficacious.

Epidemiology of melasma in Brazilian patients: a multicenter study

Melasma is an acquired, irregularly patterned, light to dark-brown hypermelanosis, with symmetric distribution mostly over the face. The aim of this study was to evaluate clinical characteristics and factors related to melasma in Brazilian patients. This was a cross-sectional, multicenter study performed in Brazil. Investigators examined and questioned 953 patients over 18 years of age on clinical characteristics and other factors related to their melasma. Melasma was more prevalent in women (97.5%) and in Fitzpatrick skin phototypes II (12.8%), III (36.3%), and IV (39.7%). Skin phototypes II and III and family history of melasma had early onset of the disorder when compared with skin phototypes IV, V, and VI (P<0.0001). Similar results were also observed when these same groups were compared with the absence of family history (P<0.0001). Extra-facial melasma was more frequent in postmenopausal women compared with those who were not experiencing menopause (14.2% vs. 3.5%, P<0.0001). Data suggested that the age of melasma onset are related to skin phototypes and family history. Additionally, extra-facial melasma was more common in menopausal women. This is the first study on the epidemiology of melasma in Brazil involving a large sample of the population. These data can be a source of new relevant research on the cause and development of melasma.

Impact of 2010 Ghent criteria and subgroups definition to optimize diagnosis, avoid aortic dissection and choose the right surgical timing in the experience of the Tor Vergata Marfan Centre registry

Purpose: Aim of this study was to verify how Marfan Syndrome (MFS) patients followed by our Centre were distributed in the different subgroups highlighted by new 2010 Ghent nosology: 3 in the presence of family history (FH), FH and aortic dilatation (Ao), FH e score system ≥7 (SS), FH and ectopia lentis (EL), 4 in the absence of family history (Ao e EL, Ao e SS, Ao e FBN1, EL e FBN1 mutation) and to define the impact of aortic root dilatation in the diagnosis of the syndrome to support a cardiac surgery department's management of a Marfan Diagnostic Centre. Methods: We reviewed clinical features of 500 subjects visited in our Centre from January 2008 to December 2012; 146 patients (74 men and 72 women) had MFS clinical diagnosis. The population included 29 children (age 40 y). All patients was submitted to echocardiographic exam and measurement of aortic root along the American Society of Echocardiography guidelines, genetic advice, orthopedic visit, eye and dental examination and pediatric counseling, the last for patients younger than 14 y. In all cases spine and hips X-ray were performed. Results: In presence of family history 78 patients (53%) were in FH and Ao subgroup, 8 patients (5,4%) in FH and SS and 3 (2%) in FH and EL. In 45 patients the was no FH and the diagnosis was possible for the concomitance of Ao and EL in 33 patients (22%), of Ao and SS in 20 (13%), in 2 cases (1,3%) for Ao and FBN1 mutation, and in 2 cases (1,3%) for EL and FBN1 gene mutation. Among the 78 patients with FH, 32 belong to one big kin family with high incidence of sudden cardiac death for dissection. Main characteristics in our population were aortic dilation with Z-score ≥2 in adults and ≥3 in children present in 133 (91%) patients, FH in 89 (61%), SS≥7 in 55 (37%), ectopia lentis in 36 (24%), the FBN1 mutation response was present in 31 (21%). Fifty-four patient (37%) underwent to cardiac surgery, 50 patient for aortic root replacement and 4 patients for mitral valve procedure. We had no deaths for aortic dissection in 4 years of observation. Conclusions: New 2010 Ghent Criteria allow an excellent clinical definition of MFS and a rapid diagnosis thanks the possibility to include patients in a specific subgroup. Aortic dilation was the main feature of our population. A clear diagnosis and a cardiac surgery vision of follow-up are crucial for an optimal management and surgical decision.

The Knowledge of Colorectal Cancer Symptoms and Risk Factors among 10,078 Screening Participants: Are High Risk Individuals More Knowledgeable?

ObjectivesWe tested the a priori hypothesis that self-perceived and real presences of risks for colorectal cancer (CRC) are associated with better knowledge of the symptoms and risk factors for CRC, respectively.MethodsOne territory-wide invitation for free CRC screening between 2008 to 2012 recruited asymptomatic screening participants aged 50–70 years in Hong Kong. They completed survey items on self-perceived and real presences of risks for CRC (advanced age, male gender, positive family history and smoking) as predictors, and knowledge of CRC symptoms and risk factors as outcome measures, respectively. Their associations were evaluated by binary logistic regression analyses.ResultsFrom 10,078 eligible participants (average age 59 years), the mean knowledge scores for symptoms and risk factors were 3.23 and 4.06, respectively (both score range 0–9). Male gender (adjusted odds ratio [AOR] = 1.34, 95% C.I. 1.20–1.50, p<0.01), self-perception as not having any risks for CRC (AOR = 1.12, 95% C.I. 1.01–1.24, p = 0.033) or uncertainty about having risks (AOR = 1.94, 95% C.I. 1.55–2.43, p<0.001), smoking (AOR 1.38, 95% C.I. 1.11–1.72, p = 0.004), and the absence of family history (AOR 0.61 to 0.78 for those with positive family history, p<0.001) were associated with poorer knowledge scores (≤4) of CRC symptoms. These factors remained significant for knowledge of risk factors.ConclusionsMale and smokers were more likely to have poorer knowledge but family history of CRC was associated with better knowledge. Since screening of these higher risk individuals could lead to greater yield of colorectal neoplasm, educational interventions targeted to male smokers were recommended.

Multifocal Breast Cancer in Young Women with Prolonged Contact between Their Breasts and Their Cellular Phones.

Breast cancer occurring in women under the age of 40 is uncommon in the absence of family history or genetic predisposition, and prompts the exploration of other possible exposures or environmental risks. We report a case series of four young women—ages from 21 to 39—with multifocal invasive breast cancer that raises the concern of a possible association with nonionizing radiation of electromagnetic field exposures from cellular phones. All patients regularly carried their smartphones directly against their breasts in their brassieres for up to 10 hours a day, for several years, and developed tumors in areas of their breasts immediately underlying the phones. All patients had no family history of breast cancer, tested negative for BRCA1 and BRCA2, and had no other known breast cancer risks. Their breast imaging is reviewed, showing clustering of multiple tumor foci in the breast directly under the area of phone contact. Pathology of all four cases shows striking similarity; all tumors are hormone-positive, low-intermediate grade, having an extensive intraductal component, and all tumors have near identical morphology. These cases raise awareness to the lack of safety data of prolonged direct contact with cellular phones.

Aortic Disease in the Young: Genetic Aneurysm Syndromes, Connective Tissue Disorders, and Familial Aortic Aneurysms and Dissections

There are many genetic syndromes associated with the aortic aneurysmal disease which include Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), Loeys-Dietz syndrome (LDS), familial thoracic aortic aneurysms and dissections (TAAD), bicuspid aortic valve disease (BAV), and autosomal dominant polycystic kidney disease (ADPKD). In the absence of familial history and other clinical findings, the proportion of thoracic and abdominal aortic aneurysms and dissections resulting from a genetic predisposition is still unknown. In this study, we propose the review of the current genetic knowledge in the aortic disease, observing, in the results that the causative genes and molecular pathways involved in the pathophysiology of aortic aneurysm disease remain undiscovered and continue to be an area of intensive research.

Acrokeratosis verruciformis of hopf along lines of blaschko

Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis presenting as multiple plane wart-like lesions symmetrically distributed on dorsum of hands and feet. Its pathogenesis is unknown. A case of 24 years old female is described with multiple hyperpigmented, hyperkeratotic papules on the left side of body since 5 years along the lines of Blaschko. Histopathology showed changes of AKV. Other unusual findings were the absence of family history, extensive lesions with flexural, and genital involvement.

Segmental Lentiginosis and Hypomelanosis of Ito with Bilateral Lisch Nodules: Is it an Unusual Presentation of Segmental Neurofibromatosis?

Observation: We here report a 16 year-old Turkish girl with an unusual combination of hiperpigmented macules and hypopigmented patch on her right face and neck region with a sharp demarcation to the midline. Her mother defined that they had first appeared when she was two years old. Bilateral lisch nodules in both eyes were determined through the ophthalmologic examination. While histopathology of a brown macule revealed the features of lentigo and hypopigmented patch showed the features of hypomelanosis of Ito the diagnosis of segmental (NF) was made on the basis of these clinical features and the absence of family history and systemic involvement. However bilateral Lisch nodules were found to be a rare accompanying disorder in segmentel NF, we suggest that our patient have a subtype of this entity. Although we could not demonstrate the genetic mutation, the clinical and histopathological findings indicate us the somatic mosaicism.

Family history in early-onset inflammatory bowel disease

Springer 2012 Kuwahara and colleagues [1] recently published in your journal an original paper entitled ‘‘Effects of family history on inflammatory bowel disease (IBD) characteristics in Japanese patients’’. Ulcerative colitis (UC) and Crohn’s disease (CD) are the two main forms of IBD. Both UC and CD are complex and heterogeneous multifactorial diseases in which both hereditability and environment (behavioral and microbial factors) contribute to the development of the diseases [2]. Kuwahara et al. [1] performed an epidemiological study considering present age, age at disease onset, and family history (FH) in Japanese IBD patients. The authors clearly show that in some aspects the characteristics of IBD vary according to the presence or absence of FH. In particular, in patients with UC, present age and age at disease onset were significantly lower if they had an FH. This result was not observed in patients with CD. Regarding the lack of association between FH and age at disease onset in CD patients, however, it should be noted that the study did not include patients with very early-onset CD (before 5 years of age), which might represent an interesting group of patients for the study of FH and age at disease onset. In our experience [3, 4] in the case of very early-onset CD, Mendelian genetics, linkage analysis, and familial studies can contribute to the identification of new private mutations and novel candidate genes. Otherwise, by considering CD as a complex condition, other approaches based on association studies in populations have been commonly adopted to evaluate the incidence of the disease. Furthermore, the samples of UC and CD cases analyzed by Kuwahara and colleagues were heterogeneous not only in terms of numbers of patients considered (46,114 cases of UC and 11,305 cases of CD), but in particular in the distribution of younger ages, which is crucial for understanding the role of FH. In conclusion, we found the study results to be very interesting. We believe, however, that studying the FH of very early-onset CD may provide significant help to clarify the role of the genetic component in the onset of CD. In our opinion the power of genetic studies increases when focusing on children, as they show higher gene dosage effects [5] and fewer environmental influences [6].

Pseudohypoparathyroidism: A Case Report of a Rare Disease with Uncommon Presentation Producing Diagnostic Dilemma

Pseudohypoparathyroidism (PHP) is a rare hereditary disorder having the prevalence of 3.4 per million. It is characterized by symptoms and signs of hypoparathyroidism, typically in association with distinctive skeletal and developmental defects. The features of hypoparathyroidism are due to tissue resistance to the effect of parathyroid hormone (PTH). We will describe a 32-yearold woman who had recurrent convulsion for 16 years, infertility, cataract, psychosis, candidiasis and typical features of Albright’s hereditary osteodystrophy (AHO), which include a round face, short neck, short stature and brachydactyly. Laboratory investigations showed hypocalcemia, hyperphosphatemia with high PTH level. Computed tomography scan of head revealed wide spread calcification in basal ganglia and cerebral hemispheres. X ray of left foot showed short left 4th metatarsal bone. The patient was diagnosed as a case of PHP on the basis of somatic features of AHO with typical biochemical abnormalities and uncontrolled convulsion with combined antiepileptic drugs for 16 years. The unusual features in our case are long delay in clinical diagnosis and absence of family history. She was treated with calcium salt and vitamin D. With this treatment patient’s condition was improved and she experiences no attack of convulsion and carpal spasm. Anticonvulsants were withdrawn gradually. We recommend that hypocalcaemia should be excluded before commencing anticonvulsant therapy in all epileptic patients and those patients whose seizures are refractory to anticonvulsant drugs DOI: http://dx.doi.org/10.3329/jbcps.v29i4.11331 J Bangladesh Coll Phys Surg 2011; 29: 227-230

A novel mutation I215V in the PRNP gene associated with Creutzfeldt–Jakob and Alzheimer’s diseases in three patients with divergent clinical phenotypes

Genetic human prion diseases are autosomal dominant disorders associated with different mutations in the PRNP gene that are manifested as distinct clinical phenotypes. Here, we report a new pathogenic missense mutation (c.[643A>G], p.[I215V]) in the PRNP gene associated with three pathologically confirmed cases: two of Creutzfeldt-Jakob disease (CJD) and one of Alzheimer's disease (AD) in two different families from the same geographical region in Spain. This mutation has not been found in any of more than 2,000 control cases studied. It represents a conservative amino acid change, and the same change is observed in the PRNP gene from other species. The two CJD cases were homozygous at codon 129 (M/M), but showed divergent clinical phenotypes with onset at ages 55 and 77 years and illness durations of 15 and 6 months, respectively. The postmortem neuropathological analysis of these cases showed homogeneous features compatible with CJD. Interestingly, the AD case (a brother of one of the CJD cases) was heterozygous at codon 129 (M/V). No familiar history was documented for any of the cases, suggesting a de novo mutation, or a partial, age-dependent penetration of the mutation, perhaps related to codon 129 status. This new mutation extends the list of known pathogenic mutations responsible for genetic CJD, reinforces the clinical heterogeneity of the disease, and advocates for the inclusion of PRNP gene examination in the diagnostic workup of patients with poorly classifiable dementia, even in the absence of family history.

Solitary rectal cap polyp: Case report and review of the literature

Rectal bleeding combined with the presence of a rectal mass has been traditionally associated with the presence of malignant disease. Cap polyposis is a relatively young and still undefined rare entity which mainly involves the rectosigmoid. It is characterized by the presence of inflammatory polyps. In this case report, we present a patient who was diagnosed with a solitary cap polyp of the rectum during the investigation of a bleeding rectal mass. The patient's age and the absence of family history were not in favor of malignancy, despite the strong initial clinical impression. After confirmation of the diagnosis, the patient underwent a snare excision and remains asymptomatic. Cap polyposis, although rare, should be suspected and, when diagnosed, should be treated according to location, number of polyps and severity of symptoms.

Genetic prion disease with codon 196 PRNP mutation: clinical and pathological findings

Ten percent to 15% of all human transmissible spongiform encephalopathy are characterized by a mutation in prion protein gene (PRNP). They are distinct with respect to clinical signs, disease onset, disease duration, and diagnostic findings. During our surveillance activities in Germany, we identified 7 patients with the rare mutation E196K in PRNP gene, thereof 4 patients belonging to 2 families. The clinical syndromes were characterized by nonspecific and psychiatric symptoms at disease onset and progressed to predominant motor signs. These patients showed a late median disease onset of 71 years and short disease duration of 6.5 months. In absence of family history, they mimicked sporadic Creutzfeldt-Jakob disease (CJD). In clinical tests they were 100% positive for 14-3-3 protein detection in cerebrospinal fluid and less sensitive for magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities. As a secondary magnetic resonance imaging (MRI) abnormality, we have seen conspicuous common involvement of the subcortical white matter in 57%. Four patients underwent autopsy-pathological lesions revealed striking similarity to sporadic Creutzfeldt-Jakob disease but also involvement of the white matter.

Bilateral second branchial cleft sinuses: An unusual case report and review of the literature

Conclusion Bilateral branchial cleft anomalies are rare and can exist in the absence of family history and or syndromic associations as seen in the patient presented here However, it is important to rule out other such associations in the work up of these patients. Understanding the branchial arch embryology helps us to better understand its anatomy and allows for safe excision. In addition, preoperative imaging can also help in operative planning and confirms the clinical diagnosis. If diagnosed at a young age, prophylactic surgical excision is recommended. Introduction

Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females

Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation. © 2010 Wiley-Liss, Inc.

Very early-onset frontotemporal dementia with no family history predicts underlying fused in sarcoma pathology

Sir, Neumann et al . (2009) recently described a new subtype of frontotemporal lobar degeneration (FTLD). They examined 15 cases of FTLD with inclusions that stained positive for ubiquitin (FTLD-U) but not transactive response DNA-binding protein (TDP-43), and found positive staining for the fused in sarcoma (FUS) protein in all cases. Interestingly, this case series was also characterized by an early age of onset and absence of family history. The mean age of onset was 38 years, and 12 out of the 15 cases had an age of onset of ≤40 years (Mackenzie et al. , 2008; Roeber et al. , 2008). Since this early age of onset is highly unusual for frontotemporal dementia (Neary et al. , 2005), we hypothesized that an age of onset at ≤40 years, in the absence of a family history, could also predict underlying FUS pathology. We tested this hypothesis by reviewing the Sydney Brain Bank. …

Huntington disease in a nonagenarian mistakenly diagnosed as normal pressure hydrocephalus

In the absence of family history or overt chorea, the protean manifestations (cognitive, motor and behavioral) of Huntington disease (HD) may suggest alternative disease processes, particularly in elderly patients. Herein, we report on a nonagenarian with HD who did not manifest overt chorea until 91 years of age and was mistakenly diagnosed with normal pressure hydrocephalus at 89 years of age. The gait abnormalities seen in early HD should be readily distinguished from those of normal pressure hydrocephalus.