Three-Decade Investigation of Familial Pheochromocytoma

Tisherman, S; Tisherman, Barbara G.; Tisherman, Samuel A.; Dunmire, Susan; Levey, Gerald S.; Mulvihill, John J.

doi:10.1001/archinte.1993.00410220046005

Cited by 28 publications

(5 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Family 1 presently consists of 108 at‐risk members over seven generations. Phenotype was previously described for 19 affected members [Tisherman et al, 1993]. Although an updated description of the current 49 gene carriers is detailed separately (manuscript in preparation), results pertinent to the present family comparison of pheo expression are highlighted below.…”

Section: Resultsmentioning

confidence: 99%

“…Members of two different VHL type 2A families, each of German descent, have been followed for decades at our institution. Family 1, first described in 1962 [Tisherman et al, 1962], was found to have a T334C germline mutation (T547C in old nomenclature, codon Y112H [Mulvihill et al, 1997]) and is the largest known VHL kindred with pheo (>1,000 members when last described [Tisherman et al, 1993]). We recently performed a 50‐year update of Family 1 phenotype (manuscript in preparation) which originates from east central Germany.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genotype–phenotype correlations of pheochromocytoma in two large von Hippel–Lindau (VHL) type 2A kindreds with different missense mutations

Nielsen

Rubinstein

Thull

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Von Hippel–Lindau (VHL) disease type 2A is an inherited tumor syndrome characterized by predisposition to pheochromocytoma (pheo), retinal hemangioma (RA), and central nervous system hemangioblastoma (HB). Specific VHL subtypes display genotype–phenotype correlations but, unlike other familial syndromes such as MEN-2, the phenotype in VHL has not yet been stratified at the codon level. Over decades, we have managed two very large VHL type 2A regional kindreds with nearly adjacent but distinct VHL missense mutations. We determined the phenotype of Family 2 and compared the clinical and pathologic parameters of pheo between 30 members of Family 1 (Y112H mutation) and 33 members of Family 2 (Y98H mutation) with mean follow-up of 15.5 and 12.1 years, respectively (P=0.24). In Family 2, pheo was the most frequent VHL manifestation (79%) and all pheo diagnoses occurred by age 50. Age at first diagnosis was younger in Family 2 than in Family 1 (mean 19.7 vs. 28.8 years; P=0.02). Pheo expressivity differed by genotype: Family 1 pheo was more likely to be multifocal (P=0.04), as well as malignant (P<0.01) and lethal (P=0.02). Family 1 pheo was also more likely to secrete vanillylmandelic acid (VMA) alone (P=0.05). This analysis of 130 pheochromocytomas in 63 VHL type 2A patients demonstrates that mutation-specific malignancy and expression patterns exist within the VHL type 2A subtype, and provides information that may help tailor the screening and management algorithms of affected members and those at risk.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotype–phenotype correlations of pheochromocytoma in two large von Hippel–Lindau (VHL) type 2A kindreds with different missense mutations

Nielsen

Rubinstein

Thull

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Here we describe the current phenotype of a kindred with VHL type 2A with a very high rate of Pheo or PGL (77-89%) without previously reported RCC or C [12][13][14]. It is the largest known kindred with familial Pheo [13] and was identified in 1962 by Samuel E. Tisherman, who as a medical resident cared for a 21 year-old man with Pheo and 4 family members with the same rare condition [12].…”

Section: Introductionmentioning

confidence: 99%

“…It is the largest known kindred with familial Pheo [13] and was identified in 1962 by Samuel E. Tisherman, who as a medical resident cared for a 21 year-old man with Pheo and 4 family members with the same rare condition [12]. Dr. Tisherman traced the family's roots to the German town of Leipzig in Saxony, from whence the original 11 siblings had immigrated to America around 1670.…”

Section: Introductionmentioning

confidence: 99%

“…Over decades, and often by means of summer picnics, Dr. Tisherman and his own family met with and evaluated [522 descendants, relying initially on blood pressure assessment and later incorporating biochemical screening and radiographic imaging. He determined that VHL was expressed in only 3/11 founder branches, containing 19 known affected members [13]. In 1997 the family was identified to carry a germline VHL missense mutation (Y112H; previously T547C) [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long-term outcomes, branch-specific expressivity, and disease-related mortality in von Hippel-Lindau type 2A

et al. 2011

View full text Add to dashboard Cite

Although a large kindred with familial pheochromocytoma (Pheo) and paraganglioma (PGL) was discovered in 1962 and later found to represent von Hippel-Lindau (VHL) type 2A (mutation Y112H), the phenotype lacks current characterization. Branch-specific expressivity was suspected based on oral family history. Family pedigree analysis, prospective interviews, and extensive record review were used to extend the pedigree, determine phenotype, examine branch-specific expression, and analyze mortality rates over 5 decades. In its 3 known affected branches the kindred now comprises 107 people with or at-risk for VHL, of whom 49 have been diagnosed and 35/49 (71%) are clinically affected. Phenotypic cumulative lifetime risk was 71% for Pheo/PGL, 15% for hemangioblastoma, 33% for retinal angioma, 3% for renal cell carcinoma, and 3% for pancreatic cysts. The mean ages for VHL and Pheo/PGL diagnosis were younger in successive generations. Branch II-4 predominately expressed RA, while branch II-5 predominantly expressed Pheo/PGL. Disease-specific mortality occurred early and was less frequent in successive generations. This analysis of Y112H VHL confirms a high cumulative risk for pheochromocytoma/paraganglioma. Over time, both age at diagnosis and disease-specific mortality have decreased. The observed branch-specific expressivity prompts further study of genetic and environmental disease modifiers in this large family.

show abstract

Familial Pheochromocytoma Due to Mutant von Hippel-Lindau Disease Gene

Mulvihill¹

1997

Arch Intern Med

View full text Add to dashboard Cite

726 patients) had hyperthyroidism, and 35 (4.8%) more may have had hypothyroidism. Even if all these patients represent subclinical thyroid disease, it is important to rec¬ ognize these patients. Patients with hyperthyroidism, even subclinical forms, are at a greater risk for recurrent atrial fibrillation, osteopenia, and iodine-induced clinical hy¬ perthyroidism. Patients treated during subclinical hypo¬ thyroidism show improved symptom and psychometric testing scores.3 Patients with atrial fibrillation should also undergo testing for hyperlipidemia and coronary artery dis¬ ease, conditions that overlap in the need to be tested for thyroid status. It is unfortunate that proper follow-up re¬ ports are not available on the tested subjects.During the course of the study, serum thyrotropin level testing replaced free thyroxine analysis, a strategy that is supported by the literature4 but is more expen¬ sive. It is also more accurate, however, particularly in the hospitalized sick population, such as the one under study. Even using the data in the study by Krahn et al,1 it cost them $ 1760 to find each new patient with hyperthyroid¬ ism, a figure far lower than other acceptable costeffectiveness assessments,5,6 in which costs as high as $26 130 per quality-adjusted life-year (1994 dollars) are considered worthwhile investments.To answer the question of what test strategies are effective to assess patients with recent-onset atrial fibril¬ lation requires better exclusion and inclusion criteria and better data analysis than that supplied by Krahn et al.1The letter by Schreiber calls into question the methodology and presentation of our data on the results ofthyroid screening in 726 patients with recent-onset atrial fibrillation.1 This article attempted to determine the yield of routine screening in this population with a discussion of the resultant utility and cost implications. The first concern revolves around patient selection for the Canandian Registry of Atrial Fibrillation study.1 Indeed, patients with transient atrial fibrillation surrounding cardiac surgery or other procedures warrant attention, but the purpose of this database was to establish the natural history of atrial fibrillation with current therapy in a patient population at significant risk for recurrent atrial fibrillation. These data do not necessarily generalize to all patients with atrial fibrillation, the management of which must be tailored to the individual clinical presentation. Second, Table 2 suggests that 18 patients had previous hyperthyroidism (6 taking thyroxine) and 44 patients had previous hypothyroidism (37 taking thyroxine). The text discusses those patients with abnormal serum thyrotropin levels and their preceding clinical thyroid history but does not discuss the patients with previous thy¬ roid disease and biochemical euthyroidism on enrollment.Third, the follow-up in patients with abnormal results of the thyroid screening was arranged at the dis¬ cretion of the patient's physician and as such was not routine in the sense that pat...

show abstract

Three-Decade Investigation of Familial Pheochromocytoma

Cited by 28 publications

References 17 publications

Genotype–phenotype correlations of pheochromocytoma in two large von Hippel–Lindau (VHL) type 2A kindreds with different missense mutations

Genotype–phenotype correlations of pheochromocytoma in two large von Hippel–Lindau (VHL) type 2A kindreds with different missense mutations

Long-term outcomes, branch-specific expressivity, and disease-related mortality in von Hippel-Lindau type 2A

Familial Pheochromocytoma Due to Mutant von Hippel-Lindau Disease Gene

Contact Info

Product

Resources

About