Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants

2021 ◽  
pp. jmedgenet-2021-107954
Author(s):  
Clément Desjardins ◽  
Frédéric Caux ◽  
Bertrand Degos ◽  
Djallel Benzohra ◽  
Astrid De Liège ◽  
...  
Keyword(s):  
Social Cognition ◽  
Neuropsychological Assessment ◽  
Splice Site ◽  
Autosomal Dominant ◽  
Neuropsychological Functioning ◽  
Cowden Syndrome ◽  
Increased Risk ◽  
Cerebral Mri ◽  
Dominant Disease ◽  
Brain Alteration

PurposeCowden syndrome (CS) is an autosomal dominant disease related to germline PTEN variants and is characterised by multiple hamartomas, increased risk of cancers and frequent brain alteration. Since the behaviour of patients with CS sometimes appears to be inappropriate, we analysed their neuropsychological functioning.MethodsThis monocentric study was conducted between July 2018 and February 2020. A standardised neuropsychological assessment, including an evaluation of social cognition, executive functions, language and dexterity, as well as a cerebral MRI were systematically proposed to all patients with CS. Moreover, PTEN variants were identified.ResultsFifteen patients from 13 families were included, with six non-sense (40%), three missense (20%), five frameshift (33.3%) and one splice site (6.6%) variant types. Twelve patients (80%) had altered social cognition: 10 patients had an abnormal modified Faux-Pas score and 5 had Ekman’s facial emotions recognition impairment. Nearly all patients (93%) had impaired dexterity. Cerebral MRI showed various cerebellar anomalies in seven patients (46.7%).ConclusionAltered social cognition and impaired fine dexterity are frequently associated with CS. Further studies are needed to confirm these results and to determine whether dexterity impairment is due to the effect of germline PTEN variants in the cerebellum.

scholarly journals Characteristics of Small Bowel Polyps Detected in Cowden Syndrome by Capsule Endoscopy

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Keita Saito ◽  
Eiki Nomura ◽  
Yu Sasaki ◽  
Yasuhiko Abe ◽  
Nana Kanno ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Small Bowel ◽  
Capsule Endoscopy ◽  
Autosomal Dominant ◽  
Cowden Syndrome ◽  
Malignant Diseases ◽  
Double Contrast ◽  
Hamartomatous Polyps ◽  
X Ray ◽  
Dominant Disease

Cowden syndrome is an uncommon, autosomal dominant disease characterized by multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases are reportedly complicated by malignant diseases. Hamartomatous polyps occur throughout the gastrointestinal tract, the most common sites being the stomach, colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome; however, they are difficult to detect by conventional examination, including double-contrast X-ray study. Here, we report three cases of Cowden syndrome with small bowel polyps, which were detected by capsule endoscopy. The small bowel polyps of Cowden syndrome frequently occur at the oral end of the small bowel, especially in the duodenum and jejunum, and their color is similar to that of the surrounding mucosa; additionally, the polyps are relatively small (2–5 mm). Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome.

Pancreatic Manifestations of von Hippel-Lindau Disease

2010 ◽  
Vol 134 (7) ◽  
pp. 1080-1083
Author(s):  
Anthony-Osei F. Safo ◽  
Stefan E. Pambuccian
Keyword(s):  
Autosomal Dominant ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Increased Risk ◽  
Vascular Neoplasms ◽  
High Penetrance ◽  
Dominant Disease ◽  
Von Hippel Lindau Disease ◽  
The Central Nervous System

Abstract Von Hippel-Lindau disease is an uncommon, multisystem, multitumor disorder that can present in sporadic form but is more commonly inherited as an autosomal-dominant disease with high penetrance. Affected patients are at increased risk for developing multiple synchronous or metachronous benign or malignant, cystic, and vascular neoplasms of various organs. The characteristic neoplasms associated with von Hippel-Lindau are hemangioblastoma of the central nervous system and retina, clear cell renal cell carcinoma, and pheochromocytoma, but other lesions are well recognized. Pancreatic lesions, both primary and metastatic, are common, and several differential diagnostic possibilities must be considered.

scholarly journals Peutz-Jeghars’ syndrome, a rare genetic disorder: A case report

2020 ◽  
Vol 3 (7) ◽  
Author(s):  
Fabia Hannan Mone ◽  
Kuntal Roy ◽  
Gazi Zahirul Hasan, ◽  
Kaushik Roy ◽  
Qazi Sazib Ahamed, ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Hamartomatous Polyps ◽  
Gastrointestinal Malignancy ◽  
Increased Risk ◽  
Hamartomatous Polyposis Syndromes ◽  
Mucocutaneous Pigmentation ◽  
Dominant Disease ◽  
Polyposis Syndromes ◽  
Peutz Jeghers Syndrome

Abstract: Hamartomatous polyposis syndromes or Peutz-Jeghers syndrome (PJS) is a hereditary autosomal dominant disease characterized by benign hamartomatous polyps and mucocutaneous pigmentation in the digestive tract. It occurs mostly in the small intestine during first decade of life but frequently in the colon and stomach. Only a few cases have been reported in the duodenum1. Polyposis syndromes are common cause of adult intussusceptions, with polyps acting as lead points. Adult intussusceptions are rare and is almost always associated with that lead point2. Although hamartomatous polyps are not pre-malignant, there is an increased risk of gastrointestinal and non-gastrointestinal malignancy, commonly involving the small bowel. Most patients of PJS presents with acute abdomen and diagnosed as intussusceptions, commonly entero-enteric type but colo-colic intussusceptions are rare in Peutz-Jeghers syndrome3. To the best of our knowledge, synchronous colo-colic intussusception association in Peutz-Jeghers syndrome has not been previously reported.

scholarly journals A family harboring an MLKL loss of function variant implicates impaired necroptosis in diabetes

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Joanne M. Hildebrand ◽  
Bernice Lo ◽  
Sara Tomei ◽  
Valentina Mattei ◽  
Samuel N. Young ◽  
...  
Keyword(s):  
Potential Role ◽  
Autosomal Dominant ◽  
Inflammatory Diseases ◽  
Diabetic Patients ◽  
Incomplete Penetrance ◽  
Loss Of Function ◽  
Healthy Sibling ◽  
Dominant Disease ◽  
Terminal Effector

AbstractMaturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL−/− human cell lines. This MLKL mutation may act as a modifier to the P33T PDX1 mutation, and points to a potential role of impairment of necroptosis in diabetes. Our findings highlight the importance of family studies in unraveling MODY’s incomplete penetrance, and provide further support for the involvement of dysregulated necroptosis in human disease.

scholarly journals Founder Effect of a c.828+3A>T Splice Site Mutation in Peripherin 2 (PRPH2) Causing Autosomal Dominant Retinal Dystrophies

2015 ◽  
Vol 133 (5) ◽  
pp. 511 ◽  
Author(s):  
Suma P. Shankar ◽  
David G. Birch ◽  
Richard S. Ruiz ◽  
Dianna K. Hughbanks-Wheaton ◽  
Lori S. Sullivan ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Dominant ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Retinal Dystrophies

scholarly journals PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3120
Author(s):  
David D. Dragoo ◽  
Ahmed Taher ◽  
Vincenzo K. Wong ◽  
Ahmed Elsaiey ◽  
Nikita Consul ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Malignant Tumors ◽  
Cowden Syndrome ◽  
Benign Tumors ◽  
Imaging Findings ◽  
Pten Hamartoma Tumor Syndrome ◽  
Associated Lesions ◽  
Tumor Recognition ◽  
Integral Role ◽  
Early Tumor

PTEN hamartoma tumor syndrome/Cowden syndrome (CS) is a rare autosomal dominant syndrome containing a germline PTEN mutation that leads to the development of multisystem hamartomas and oncogenesis. Benign tumors such as Lhermitte–Duclos disease and malignant tumors involving the breast, thyroid, kidneys, and uterus are seen in CS. Radiologists have an integral role in the comanagement of CS patients. We present the associated imaging findings and imaging screening recommendations. Knowledge of the types of cancers commonly seen in CS and their imaging findings can aid in early tumor recognition during cancer screening to help ensure near-normal life spans in CS patients.

scholarly journals A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Saba Ahmad ◽  
Luis Manon ◽  
Gifty Bhat ◽  
Jerry Machado ◽  
Alice Zalan ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cellular Differentiation ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Disease ◽  
Sacrococcygeal Teratoma ◽  
Dominant Disease ◽  
The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

scholarly journals Clinical case of myocardial infarction with unspecified familial hypercholesterolemia

2022 ◽  
Vol 17 (4) ◽  
pp. 74-78
Author(s):  
N. G. Lozhkina ◽  
A. N. Spiridonov
Keyword(s):  
Myocardial Infarction ◽  
Familial Hypercholesterolemia ◽  
Clinical Case ◽  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Cholesterol Metabolism ◽  
Single Gene ◽  
Low Density Lipoproteins ◽  
Dominant Disease ◽  
Appropriate Therapy

Familial hypercholesterolemia is a hereditary autosomal dominant disease characterized by a violation of cholesterol metabolism. This nosology was first described in the late 1930s by the Norwegian clinician Karl Moeller, he proposed the idea that hypercholesterolemia and tendon xanthomas are associated with cardiovascular diseases through the inheritance of a single gene. In 1964, two clinical phenotypes of familial hypercholesterolemia were discovered: heterozygous and homozygous, associated with an unfavorable prognosis. To date, it is known that the long-running process of accumulation of low-density lipoproteins in the intima of blood vessels may not have clinical symptoms for many years due to the developed system of collaterals and the absence of hemodynamically significant stenosis. However, without timely diagnosis and appropriate therapy, this condition inevitably leads to the development of a cardiovascular event. The article presents a clinical case demonstrating the development of myocardial infarction in a patient with a late diagnosis of this disease.

scholarly journals A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy

Brain ◽  
2006 ◽  
Vol 130 (4) ◽  
pp. 1029-1042 ◽  
Author(s):  
M. V. Alavi ◽  
S. Bette ◽  
S. Schimpf ◽  
F. Schuettauf ◽  
U. Schraermeyer ◽  
...  
Keyword(s):  
Splice Site ◽  
Optic Atrophy ◽  
Autosomal Dominant ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Autosomal Dominant Optic Atrophy ◽  
Dominant Optic Atrophy ◽  
Opa1 Gene

DLX3 Mutation in a New Family and Its Phenotypic Variations

2008 ◽  
Vol 87 (4) ◽  
pp. 354-357 ◽  
Author(s):  
S.-K. Lee ◽  
Z.H. Lee ◽  
S.-J. Lee ◽  
B.-D. Ahn ◽  
Y.-J. Kim ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Autosomal Dominant ◽  
Mutational Analysis ◽  
Enamel Hypoplasia ◽  
Enamel Defects ◽  
Clinical Phenotypes ◽  
New Family ◽  
Dominant Disease ◽  
Curly Hair ◽  
Phenotypic Variations

Tricho-dento-osseous syndrome (TDO) is an autosomal-dominant disease characterized by curly hair at birth, enamel hypoplasia, taurodontism, and a thick cortical bone. A common DLX3 gene mutation (c.571_574delGGGG) has been identified in multiple families with variable clinical phenotypes. Recently, another DLX3 gene mutation (c.561_562delCT) was reported to cause amelogenesis imperfecta with taurodontism (AIHHT). We identified a Korean family with overlapping phenotypes of TDO and AIHHT. We performed mutational analysis to discover its genetic etiology. The identified mutation was c.561_562delCT mutation in the DLX3 gene. The enamel was hypomature and hypoplastic. The characteristic taurodontic features were not identified. Increased bone density or thickness could not be revealed by cephalometric, hand-wrist, and panoramic radiographs. Affected individuals reported that their nails were brittle, and they had curly hair at birth. This study clearly showed that the c.561_562delCT mutation had not only enamel defects, but also other clinical phenotypes resembling those of TDO syndrome.

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