A Novel PRKAR1A Mutation in Korean Carney Complex Family

2011 ◽  
Vol 120 (01) ◽  
pp. 7-13 ◽  
Author(s):  
S. Rhee ◽  
H. Kwon ◽  
J. Lee ◽  
J.-T. Woo ◽  
M. Kim ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Mutational Analysis ◽  
Clinical Symptoms ◽  
Skin Pigmentation ◽  
Clinical Manifestations ◽  
Carney Complex ◽  
Type I ◽  
Endocrine Tumours ◽  
Extensive Evaluation ◽  
Family Variable

AbstractCarney complex (CNC) is an autosomal dominant hereditary or sporadic multiple neoplastic syndrome that shows variable clinical symptoms. Generally, CNC appears as skin pigmentation, cardiac or cutaneous myxomas, and multiple endocrine tumours. We performed an extensive evaluation of 9 individuals within 1 family in whom CNC was suspected. Among them, 5 had CNC with various clinical manifestations. We also performed mutational analysis of suspected genes in these patients. Although all patients were members of the same family, variable CNC-related manifestations were observed in each patient. An analysis showed a novel deletion mutation (c.537delA) in exon 6 of the PRKAR1A gene in the patients. Based on our results, the patients were determined to have CNC type I. This is the first such mutational report in Korea.

scholarly journals Carney Complex With Endocrine Involvement Isolated to the Thyroid Gland

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A992-A993
Author(s):  
Vanessa Williams ◽  
Hadoun Jabri ◽  
Michael G Jakoby
Keyword(s):  
Growth Hormone ◽  
Thyroid Gland ◽  
Thyroid Carcinoma ◽  
Multinodular Goiter ◽  
Autosomal Dominant ◽  
Skin Lesions ◽  
Carney Complex ◽  
Type I ◽  
Pigmented Lesions ◽  
Endocrine Organs

Abstract Introduction: Carney complex is a rare autosomal dominant disorder characterized by pigmented lesions of skin and mucosae, endocrine neoplasms or overactivity, and myxomas of the heart, skin, and other organs. Most patients have at least two affected endocrine organs at time of diagnosis. We present a case of Carney complex with endocrine involvement limited to the thyroid gland. Case: A 48-year-old female was referred for evaluation of thyroid nodules incidentally discovered on imaging for submandibular salivary gland swelling. Ultrasound evaluation of the thyroid revealed numerous, bilateral nodules that were mostly cystic or spongiform, though some had irregular borders and microcalcifications. A brother with Carney complex had been diagnosed with papillary carcinoma, and the patient decided to undergo thyroidectomy. Fortunately, no thyroid carcinoma was found on postsurgical histopathology. Initial biochemical evaluation showed no evidence of hypercortisolemia (8 AM cortisol 1.7 mcg/dL on 1 mg dexamethasone suppression test; 24-h urine cortisol 26.1 mcg [reference: 4-50]), growth hormone excess (IGF-1 190 ng/mL [reference: 52-328]), or hyperprolactinemia (prolactin 10 ng/mL [reference: 2.74-26.72]). Imaging showed no pituitary or adrenal masses. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer prior to referral. She was diagnosed with Carney complex at age 19 years, and her manifestations included atrial and ventricular myxomas, intraductal adenoma of the breast, multiple skin lesions (lentigines, blue nevi, and cutaneous myxomas), and myxomas of the external auditory canals. She is in a Carney complex kindred that includes her mother, two brothers, and a niece. Discussion: Carney complex is usually caused by inactivating mutations or large deletions in the protein kinase A type I alpha regulatory subunit (PRKAR1A) gene located on chromosome 17q22-24. Most mutations are inherited in an autosomal dominant manner, though approximately 30% of cases are due to de novo mutations. In a review of 365 cases, the median age at diagnosis was 20 years. Growth hormone adenomas or somatomammotroph hyperplasia occurs in approximately 75% of patients, and most have at least one additional endocrine abnormality including multinodular goiter, primary pigmented nodular adrenocortical hyperplasia, and testicular or ovarian masses. There is an approximately 10% chance of developing well differentiated thyroid carcinoma. Treatment for Carney complex is individualized depending on the patient’s presentation and includes excision or surgical removal of myxomas, neoplasms, and skin lesions, as well as regular evaluation for cardiac myxomas and endocrine overactivity. This case of Carney complex is unusual because the only endocrinopathy is multinodular goiter.

Familial Pfeiffer Syndrome: Variable Manifestations and Role of Multidisciplinary Team Care

2021 ◽  
pp. 105566562110285
Author(s):  
Sarut Chaisrisawadisuk ◽  
Mark H Moore
Keyword(s):  
Autosomal Dominant ◽  
Clinical Manifestations ◽  
Type I ◽  
Syndrome Type ◽  
Team Care ◽  
Pfeiffer Syndrome ◽  
Wide Range ◽  
Craniofacial Syndromes ◽  
Broad Thumbs

Pfeiffer syndrome is one of the autosomal dominant craniofacial syndromes. Classical clinical manifestations are coronal suture synostosis causing brachycephaly, midface retrusion, airway compromise, broad thumbs, and toes. Pfeiffer syndrome type I (classic type) is associated with FGFR1 mutation. However, wide range of clinical manifestations, with and without craniosynostosis, have been reported. Here, we present a family of Pfeiffer syndrome across 3 generations with identical FGFR1: c.755C>G (p.Pro252Arg) mutation. Where the members of the youngest generation have no cranial involvement. Lastly, we propose a guideline management for familial Pfeiffer syndrome management.

scholarly journals Apert syndrom: a literature review and own clinical case

2020 ◽  
pp. 55-58
Author(s):  
V.M. Husiev ◽  
◽  
D.S. Khapchenkova ◽  
V.E. Kleban ◽  
◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Case ◽  
Clinical Symptoms ◽  
Proximal Phalanx ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Apert Syndrome ◽  
Type I ◽  
Hands And Feet ◽  
Type V

Acrocephalosyndactyly (ACS) is a group of multiple malformations, the main clinical manifestations of which are acrocephaly and syndactyly. The most common forms are Apert (type I), Pfeiffer (type V), Setra–Hotzen (type II) syndromes. Apert syndrome is the most explored and common form of all types of ACS and Apert syndrome is estimated to occur in 1 in: 100 000 newborns. The syndrome is inherited in an autosomal dominant manner. If the gene is carried by one of the parents, the risk of having a child with Apert syndrome is 50%. The syndrome genome (FGFR2) is located on the long arm of chromosome 10 at locus 10q26. Apert syndrome occurs due to mutations at this locus, but the children karyotype is not changed. The pathognomonic clinical signs of Apert syndrome are craniofacial dysostosis and symmetrical syndactyly of the hands and feet. Acrocephaly («tower skull») — is a consequence of early synostosis of some sutures of the skull. Orbital hypertelorism and exophthalmos are referred to typical facial changes. Among other abnormalities there are heart and vascular defects (25%), cleft palate, malformations of the gastrointestinal tract and kidneys. The diagnosis is made on the basis of clinical symptoms. No treatment has been developed. Life expectancy is short. Purpose — to present a clinical case of a newborn with Apert syndrome. Clinical case. Apert syndrome was suspected prenatally, confirmed after birth. The newborn girl had the characteristic signs of the above-described pathology: «tower head», hypertelorism, saddle bridge of the nose, closed large fontanelle, phalanges of the first finger were wide, the proximal phalanx was triangular, complete cutaneous syndactyly of the II–IV fingers was observed symmetrical on both upper extremities; on the lower extremities — thickening of the proximal phalanges of the big toes, complete cutaneous syndactyly of the II–IV toes. Conclusions. The article describes a clinical case of a child with Apert syndrome. Prenatal diagnosis takes one of the leading places in confirming genetic abnormalities, determining the prognosis for life. Genetic counseling for parents is necessary and important at all stages of pregnancy planning. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: Apert syndrome, children, prenatal diagnosis.

scholarly journals Peutzo ir Jegherso sindromo klinika, diagnostika, gydymas ir klinikinis atvejis

2005 ◽  
Vol 3 (3) ◽  
pp. 0-0
Author(s):  
Orinta Marija Kviatkovskaja ◽  
Vytautas Lipnickas ◽  
Kęstutis Strupas
Keyword(s):  
Autosomal Dominant ◽  
Skin Pigmentation ◽  
Clinical Manifestations ◽  
University Hospital ◽  
Pathological Findings ◽  
Gastrointestinal Polyposis ◽  
Mild Anemia ◽  
Complicated Course ◽  
Vilnius University ◽  
Peutz Jeghers Syndrome

Orinta Marija Kviatkovskaja, Vytautas Lipnickas, Kęstutis StrupasVilniaus universiteto ligoninėsSantariškių klinikos Pilvo chirurgijos centras,Santariškių g. 2, LT-08661 VilniusEl paštas: [email protected] Šio straipsnio tikslas – aprašyti Peutzo ir Jegherso sindromo klinikinį atvejį, pateikti literatūros apžvalgą. Peutzo ir Jegherso sindromas yra reta autosominiu dominantiniu būdu paveldima liga, susijusi su dauginiais žarnyno polipais ir pigmentinėmis mukokutaninėmis dėmelėmis. Įprastai liga pasireiškia pirmą antrą gyvenimo dešimtmetį dėl polipų sukeltų virškinamojo trakto komplikacijų. Dažniausi skundai – pilvo skausmai, pykinimas, vėmimas dėl besikartojančios polipų sukeltos žarnų invaginacijos, kraujavimas iš virškinamojo trakto, tiesiosios žarnos polipo prolapsas. Be to, Peutzo ir Jegherso sindromas susijęs su didesne intra- ir ekstraintestininių piktybinių navikų rizika jauniems žmonėms, dėl to ligonius būtina nuolat stebėti. Straipsnyje pateikiame mūsų klinikoje gydyto 20 metų ligonio klinikinį atvejį. Nors klinika buvo neryški ir instrumentiniai tyrimai neinformatyvūs, buvo kritiškai įvertinta ligonio anamnezė ir pasirinkta tinkama gydymo taktika. Ligonis buvo skubos tvarka operuotas: rastos ir pašalintos trys plonosios žarnos invaginacijos. Reikšminiai žodžiai: Peutzo ir Jegherso sindromas, polipozė Peutz–Jeghers syndrome: clinics, diagnostics and management, including case report Orinta Marija Kviatkovskaja, Vytautas Lipnickas, Kęstutis StrupasCenter of Abdominal Surgery,Vilnius University Hospital "Santariškių klinikos",Santariškių str. 2, LT-08661 Vilnius, LithuaniaE-mail: [email protected] The aim of this paper is to present a rare case of Peutz–Jeghers syndrome and review the literature. Peutz–Jeghers syndrome is a rare autosomal dominant inherited syndrome associated with gastrointestinal polyposis and characteristic skin pigmentation. Typical clinical manifestations of the disease occur in the first two decades of life and are associated with complications secondary to intestinal polyps, often requiring surgical treatment. Also, patients need continuous surveillance due to a higher risk of developing intra- and extraintestinal malignancies. We present a case of young man who was operated for the fourth time due to a complicated course of the disease causing recurrent intussusceptions. There were no pathological findings on admission, except mild anemia and leukocytosis, though a thorough evaluation of the anamnesis conditioned a quick and proper management of multiple intussusceptions. Keywords: Peutz–Jeghers syndrome, polyposis

scholarly journals Clinical and mutational spectrum of 4 Chinese families with glutaric aciduria type 1

2019 ◽  
Author(s):  
Xiaorong Shi ◽  
Qiaoyan Shao ◽  
Aidong Zheng ◽  
Wenghuang Xie
Keyword(s):  
Mutational Analysis ◽  
Southern China ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Glutaric Aciduria Type ◽  
Chinese Patients ◽  
Type I ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Molecular Aspects

Abstract Background To investigate clinical presentation and molecular aspects of five patients suffered from glutaric aciduria type I (GA-I ), a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. Methods All five patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Low protein diet supplemented with special formula, GABA analog and L-carnitine were initialed following laboratory confirmation of diagnosis. The clinical and biochemical features were analyzed, and mutational analysis of GCDH was conducted using Sanger sequencing. Results Clinical manifestations of 5 patients varied from macrocephaly to severe encephalopathy, with notably different phenotype between siblings with the same mutations. Three members present complex heterozygous mutations, while two sisters present homozygous mutations. Among them, four mutations in GCDH were identified (c.1133C>T 、c.1244-2A>C 、c.339delT 、c.406G>T). Of these four mutations, c.1244- 2A>C was found in four patients and c.339delT and c.1133C>T has not yet been reported until now. Conclusions In 5 Chinese patients with GA1, two novel mutations of GCDH gene were identified, which may expand the mutation spectrum of GCDH gene. What we found confirm that there is no correlation between clinical phenotype and genotype in GA-I patients, and c.1244-2A>C may be mutation hotspot in Southern China.

scholarly journals Minireview: PRKAR1A: Normal and Abnormal Functions

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5452-5458 ◽  
Author(s):  
Ioannis Bossis ◽  
Constantine A. Stratakis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Skin Pigmentation ◽  
Suppressor Gene ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Type I ◽  
Dependent Protein ◽  
Main Component ◽  
Degree Of Differentiation

Abstract The type 1α regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA) (coded by the PRKAR1A gene) is the main component of type I PKA, which regulates most of the serine-threonine kinase activity catalyzed by the PKA holoenzyme in response to cAMP. Carney complex (CNC), or the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, is a multiple endocrine (and not only) neoplasia syndrome that is due to PRKAR1A-inactivating mutations. The R1α protein and PRKAR1A mRNA have been found to be up-regulated in a series of cell lines and human and rodent neoplasms, suggesting this molecule’s involvement in tumorigenesis and its potential role in cell cycle regulation, growth, and/or proliferation. Alterations in PKA activity elicit a variety of effects depending on the tissue, developmental stage, degree of differentiation, and cAMP levels. In addition, RIα may have functions independent of PKA. The presence of inactivating germline mutations and the loss of its wild-type allele in some CNC lesions indicate that PRKAR1A might function as a tumor suppressor gene in these tissues, but could PRKAR1A be a classic tumor suppressor gene? Probably not, and this review explains why.

scholarly journals Sepsis from Neurofibromatosis

2006 ◽  
Vol 33 (3) ◽  
pp. 328-328
Author(s):  
Navdeep Tangri ◽  
Shireen Sirhan ◽  
Gordon Crelinsten
Keyword(s):  
Autosomal Dominant ◽  
Clinical Manifestations ◽  
Neurofibromatosis Type ◽  
Large Mass ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Autosomal Dominant Disorder ◽  
Chest Wound ◽  
History Of ◽  
The Right

Neurofibromatosis Type I or von Recklinghausen’s neurofibromatosis is an autosomal dominant disorder with a high index of spontaneous mutations and extremely varied and unpredictable clinical manifestations. We present a case of sepsis secondary to an infected hematoma, enclosed within a massive neurofibroma.A 42-year-old man presented to the emergency department with a one week history of fever and chills. He reported an increase in pain and size of a growth near his chest. The patient was noted to be febrile on arrival. On physical examination, a very large neurofibroma was seen extending from the right upper chest. Wound and blood cultures were obtained. Computed Tomography (CT) of the thorax revealed a hematoma contained within the large mass.

scholarly journals Mutational analysis of the autoimmune regulator (AIRE) gene in sporadic autoimmune Addison's disease can reveal patients with unidentified autoimmune polyendocrine syndrome type I

2002 ◽  
pp. 519-522 ◽  
Author(s):  
AS Boe ◽  
PM Knappskog ◽  
AG Myhre ◽  
JI Sorheim ◽  
ES Husebye
Keyword(s):  
Mutational Analysis ◽  
Clinical Manifestations ◽  
Addison’S Disease ◽  
Addison's Disease ◽  
Common Mutation ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Regulator ◽  
Aire Gene ◽  
Autoimmune Polyendocrine Syndrome

OBJECTIVE: To investigate whether patients with Addison's disease and polyendocrine syndromes have undiagnosed autoimmune polyendocrine syndrome type I (APS I). MATERIALS AND METHODS: Forty patients with clinical manifestations resembling APS I and with autoantibodies typical of this condition were screened for Norwegian autoimmune regulator (AIRE) gene mutations. RESULTS: A 30-year old man who had developed Addison' s disease at the age of 12, but had no other components of APS I, was homozygous for the 1094-1106 deletion mutation in exon 8 of the AIRE gene, the most common mutation found in Norway. CONCLUSIONS: APS I patients with milder and atypical phenotypes are difficult to diagnose on clinical grounds. Autoantibody analysis and mutational analysis of AIRE may therefore be helpful modalities for identifying these individuals.

scholarly journals Core clinical symptoms and heterogeneous manifestations of NS / LAH: three case reports and review of the literature

2020 ◽  
Author(s):  
qiang zhang ◽  
Zailong Qin ◽  
Shaoke Chen ◽  
Xin Fan
Keyword(s):  
Short Stature ◽  
De Novo ◽  
Clinical Symptoms ◽  
Case Reports ◽  
Skin Pigmentation ◽  
Clinical Manifestations ◽  
Mapk Signaling ◽  
Molecular Characteristics ◽  
Anagen Hair ◽  
Case Presentations

Abstract Background Noonan-like syndrome with loose anagen hair-a rare autosomal dominant disease with very clinical heterogeneity, is difficult to make clinical diagnosis in the earlier period. We identified the cause of disease with severely short stature by WES on three pediatric cases. Meanwhile, we summarized the clinical manifestations of these three patients and reviewed the literature of the syndrome. Case presentations We finally confirmed three cases of Noonan-like syndrome with loose anagen hair (NS / LAH) (OMIM # 607721) and hotspot mutation in SHOC2 gene (OMIM# 602775), which both involved in the RAS-MAPK signaling pathway. The mutation located in chr10: 112724120, NM_007373.3, c.4A>G (p.Ser2Gly) is de-novo heterozygous in all patients. NS / LAH show some core clinical symptoms, such as craniofacial anomalies, short stature, weight loss, abnormal hair, growth retardation and heterogeneous manifestations (macrocephaly, GH deficiency, congenital heart disease, skin pigmentation, mental retardation, etc.). In the study, we have also proved that it is safe and feasible to apply rhGH treatent on Noonan-like syndrome with loose anagen hair. Conclusions Through our effort, we have identified a rare disease in China. The molecular characteristics, clinical manifestations, and therapeutic measure were summarized so that it can help to clinicians a better understanding of the disease and offer patients effective and timely assistance.

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