An experience with Foot Macrodactyly: A case report and review of literature

Macrodactyly is a rare congenital malformation with clinical manifestations such as enlargement of soft tissue and osseous elements. It causes various health issues such as pain, difficulty in wearing shoes, impairment in ambulatory ability and gait development, aesthetic problem, and psychological issues. The aetiology of macrodactyly is ambiguous; however, its association with PIK3CA /AKT1 genes has been reported recently. In the present study, a rare congenital macrodactyly of second and third toe of right foot along with deformed leg in 16-year-old girl has been reported. A progressive increase in the size of the second and third toe of the right foot and deformed reddish swollen area on the same lower leg below knee was seen in the patient. The malformation was present at the time of birth and at the age of one year the patient was operated for macrodactyly, but again the toe progressively increased to the previous size. She was presented with multiple health problems. There was no positive family history and/or other congenital malformation. Thus, it was suggested that due to variable phenotypic manifestations, appropriate treatment should be chosen for the patient individually.

Universal Germline Panel Testing for Individuals with Pheochromocytoma and Paraganglioma Produces High Diagnostic Yield

Background Practice guidelines to identify individuals with hereditary pheochromocytomas and paragangliomas (PPGLs) advocate for sequential gene testing strategy guided by specific clinical features and predate the routine use of multigene panel testing (MGPT). Objective To describe results of MGPT for hereditary PPGL in a clinically and ancestrally diverse cohort. Setting Commercial laboratory based in the United States. Methods Clinical data and test results were retrospectively reviewed in 1727 individuals who had targeted MGPT due to suspicion of hereditary PPGL from August 2013 through December 2019. Results Overall, 27.5% of individuals had a pathogenic or likely pathogenic variant (PV), 9.0% had a variant of uncertain significance, and 63.1% had a negative result. Most PVs were identified in SDHB (40.4%), followed by SDHD (21.1%), SDHA (10.1%), VHL (7.8%), SDHC (6.7%), RET (3.7%), and MAX (3.6%). PVs in FH, MEN1, NF1, SDHAF2, and TMEM127 collectively accounted for 6.5% of PVs. Clinical predictors of a PV included extra-adrenal location, early age of onset, multiple tumors, and positive family history of PPGL. Individuals with extra-adrenal PGL and a positive family history were the most likely to have a PV (85.9%). Restricting genetic testing to SDHB/C/D misses a third (32.8%) of individuals with PVs. Conclusion Our data demonstrate a high diagnostic yield in individuals with and without established risk factors, a low inconclusive result rate, and a substantial contribution to diagnostic yield from rare genes. These findings support universal testing of all individuals with PPGL and the use of concurrent MGPT as the ideal platform.

Development of a questionnaire to identify persons with a family history of aneurysmal subarachnoid hemorrhage

Background: Preventive screening for intracranial aneurysms is effective in persons with a positive family history of aneurysmal subarachnoid hemorrhage (aSAH), but for many relatives of aSAH patients, it can be difficult to assess whether their relative had an aSAH or another type of stroke. Aim: We aimed to develop a family history questionnaire for people in the population who believe they have a first-degree relative who had a stroke and to assess its accuracy to identify relatives of aSAH patients. Methods: A questionnaire to distinguish between aSAH and other stroke types (ischemic stroke and intracerebral hemorrhage) was developed by a team of clinicians and consumers. The level of agreement between the questionnaire outcome and medical diagnosis was pilot tested in 30 previously admitted aSAH patients. Next, the sensitivity and specificity of the questionnaire were assessed in 91 first-degree relatives (siblings/children) of previously admitted stroke patients. Results: All 30 aSAH patients were identified by the questionnaire in the pilot study; 29 of 30 first-degree relatives of aSAH patients were correctly identified. The questionnaire had a sensitivity of 97% (95% confidence interval (CI) = 83–100%) and a specificity of 93% (95% CI = 84–98%) when tested in the first-degree relatives of stroke patients. Conclusion: Our questionnaire can help persons to discriminate an aSAH from other types of stroke in their affected relative. This family history questionnaire is developed in the Netherlands but could also be used in other countries after validation.

The 2020 “Padua Criteria” for Diagnosis and Phenotype Characterization of Arrhythmogenic Cardiomyopathy in Clinical Practice

Arrhythmogenic Cardiomyopathy (ACM) is a heredo-familial cardiac disease characterized by fibro-fatty myocardial replacement and increased risk of sudden cardiac death. The diagnosis of ACM can be challenging due to the lack of a single gold-standard test: for this reason, it is required to satisfy a combination of multiple criteria from different categories including ventricular morpho-functional abnormalities, repolarization and depolarization ECG changes, ventricular arrhythmias, tissue characterization findings and positive family history/molecular genetics. The first diagnostic criteria were published by an International Task Force (ITF) of experts in 1994 and revised in 2010 with the aim to increase sensitivity for early diagnosis. Limitations of the 2010 ITF criteria include the absence of specific criteria for left ventricle (LV) involvement and the limited role of cardiac magnetic resonance (CMR) as the use of the late gadolinium enhancement technique for tissue characterization was not considered. In 2020, new diagnostic criteria (“the Padua criteria”) were proposed. The traditional organization in six categories of major/minor criteria was maintained. The criteria for identifying the right ventricular involvement were modified and a specific set of criteria for identifying LV involvement was created. Depending on the combination of criteria for right and LV involvement, a diagnosis of classic (right dominant) ACM, biventricular ACM or left-dominant ACM is then made. The article reviews the rationale of the Padua criteria, summarizes the main modifications compared to the previous 2010 ITF criteria and provides three examples of the application of the Padua criteria in clinical practice.

A mixed-ethnicity myoclonus-dystonia patient with a novel SGCE nonsense mutation: a case report

Background Myoclonus-dystonia is a rare movement disorder with an autosomal dominant inheritance pattern characterized by a combination of myoclonic jerks and dystonia that may have psychiatric manifestations. Our aim is to present neurologic and psychiatric phenotypic characteristics in the first Filipino bi-ethnic myoclonus-dystonia patient and her father. Case presentation We investigated a Filipino myoclonus-dystonia patient with a positive family history. This 21-year-old woman of mixed Filipino-Greek ethnicity presented with involuntary jerking movements of her upper extremities, head, and trunk. Her symptoms affected her activities of daily living which led her to develop moderate depression, mild to moderate anxiety, and mild obsessive-compulsive disorder (OCD). Her 49-year-old Greek father suffered from adolescence-onset myoclonus-dystonia. Conclusion Genetic testing revealed a novel epsilon-sarcoglycan (SGCE) gene nonsense mutation c.821C > A; p.Ser274* that confirmed our clinical diagnosis. For co-morbid anxiety, depression, and OCD, this patient was given duloxetine, in addition to clonazepam for the myoclonus and dystonia.

Clinical Characteristics of Female Patterned Hair Loss in Patients Attending Hair Clinic in Thailand

Objective: To study the clinical features and associated factors of female pattern hair loss (FPHL) in premenopausal and menopausal women patients. Materials and Methods: This is a retrospective chart review of FPHL patients visited hair clinic, Siriraj Hospital from June 2012 to May 2015. Demographic data, family history and history of hair loss were evaluated. Factors associated with FPHL were analysed. Results: There were 267 patients (180 premenopausal women and 87 menopausal women) in this study. The mean age of onset of patients was 35.5±12 years (premenopausal FPHL) and 60.5±7 years (menopausal FPHL). Positive family history of androgenetic alopecia (AGA) was 48.3%, mainly in first-degree relatives. The data showed an increased incidence of FPHL with advancing age. The most common presentation is Ludwig grade I. The study showed that patients also have dyslipidemia (16.9%), hypertension (16.5%), diabetes mellitus (10.9%), hypothyroidism (4.9%), anemia (3.7%), and hyperthyroidism (2.9%). In multivariate analysis, significant associations were found between low ferritin level < 70 µg/L and premenopausal FPHL (OR 5.51, 95% CI 2.26-15.14, P = 0.01). Conclusion: Maternal family history of AGA seems to have a greater influence on premenopausal FPHL. Low serum ferritin levels < 70 µg/L were significantly associated with FPHL in premenopausal women.

Clinical and Social Findings of Childhood Epilepsy

Background: Seizures are defined as a transient occurrence of signs and symptoms due to the abnormal, excessive, or synchronous neuronal activity in the brain characterized by abrupt and involuntary skeletal muscle activity. Seizure is related to specific risk factors like positive family history, fever, infections, neurological comorbidity, premature birth, mother’s alcohol abuse, and smoking in pregnancy. Epilepsy is the most frequent chronic neurologic condition in children. Studies have suggested declining incidence rates of childhood epilepsy in high-income countries during the last decades. Objective: To describe the clinical features and social findings of epilepsy in children, and to evaluate some risk factors associated with control of epilepsy. Patients and Methods: This cross-sectional study was conducted in the pediatric department of Albatool teaching hospital in Diyala province, Iraq. A total of 100 children were included in the study from February 2020 to May 2020. All children diagnosed with epilepsy in this study. Results: One hundred children with epilepsy, their mean age was 5.96± 3.33 years (range 1-14 years). Of the 48(48%) children were male and 52(52%). Of the total patients, 79% were free from seizure on AED, 21% of them were refractory to treatment.Patients without developmental delay (88.7%, p=0.012) can be controlled by AED. Patients who had idiopathic seizures (87.5%, p=0.04) can be controlled by AED. Patients who had seizure attacks can be controlled by AED more than patients who had weekly or monthly seizure attacks (97.4%) (p<0.001). Patients who had been treated by monotherapy (94.7%, p=0.012) can be controlled more than patients who were treated by multidrug therapy. Affected social interaction and need more supervision were factors that detected more in patients with refractory epilepsy, p=0.04, 0.01 respectively. While there was no association between frightened other people and epilepsy control. Conclusion: Most of the patients are characterized by: treatment approach monotherapy, less affected by social interaction and need less supervision. Patients with refractory epilepsy had opposite factors. Keywords: Epilepsy, Albatool teaching hospital.

Colorectal cancer in younger adults (<50 years); a retrospective study on its clinicopathological characteristics

Background: Colorectal cancer (CRC) is a common cancer worldwide with significant geographical variation in its incidence. CRC among young adults is not well reported in Indian patients.Methods: A retrospective study was performed to determine the burden and to analyze the clinicopathological characteristics of newly diagnosed CRC among younger adults (<50 years). Chi-square method was used to analyze the clinicopathological characteristics. P≤0.05 was considered statistically significant.Results: CRC among younger adults comprised 40.3% of total patients median age of 40 years at diagnosis, was associated with predominantly male patients with male: female ratio of 1.8:1, positive family history, lesser co-morbidities (p=0.000), majority left sided primary tumor with left: right ratio of 4.6:1, more frequent high grade histology compared to older age group (p=0.000), advanced primary tumor and nodal metastasis. Approximately one third patients had distant metastasis at diagnosis compared to in one fourth patients in older patients. Peritoneal metastasis was significantly higher among younger adults compared to older patients (p=0.000). Significantly greater proportion of patients among younger adults initially presented with bowel obstruction (p=0.034), for which upfront emergency surgical procedures was performed in significantly higher proportion of patients compared to the older age group (p=0.007).Conclusions: Advanced stage and aggressive disease biology of CRC in younger adult warrants inclusion of one decade younger age group into present screening recommendation.

Clinical, Histological, and Genetic Features of 25 Patients with Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO)/PEO-Plus Due to TWNK Mutations

Autosomal dominant mutations in the TWNK gene, which encodes a mitochondrial DNA helicase, cause adult-onset progressive external ophthalmoplegia (PEO) and PEO-plus presentations. In this retrospective observational study, we describe clinical and complementary data from 25 PEO patients with mutations in TWNK recruited from the Hospital 12 de Octubre Mitochondrial Disorders Laboratory Database. The mean ages of onset and diagnosis were 43 and 63 years, respectively. Family history was positive in 22 patients. Ptosis and PEO (92% and 80%) were the most common findings. Weakness was present in 48%, affecting proximal limbs, neck, and bulbar muscles. Exercise intolerance was present in 28%. Less frequent manifestations were cardiac (24%) and respiratory (4%) involvement, neuropathy (8%), ataxia (4%), and parkinsonism (4%). Only 28% had mild hyperCKemia. All 19 available muscle biopsies showed signs of mitochondrial dysfunction. Ten different TWNK mutations were identified, with c.1361T>G (p.Val454Gly) and c.1070G>C (p.Arg357Pro) being the most common. Before definitive genetic confirmation, 56% of patients were misdiagnosed (36% with myasthenia, 20% with oculopharyngeal muscle dystrophy). Accurate differential diagnosis and early confirmation with appropriately chosen complementary studies allow genetic counseling and the avoidance of unnecessary treatments. Thus, mitochondrial myopathies must be considered in PEO/PEO-plus presentations, and particularly, TWNK is an important cause when positive family history is present.