This mutation generates a stop codon at position and has been classified as pathogenic. We present the case of a year-old male, who was evaluated by the medical genetics service because he had noticed weakening of his voice with a high pitch since age 35, associated with premature graying since his 30s and skin lesions since about the age of At the age of 32, bilateral cataracts were diagnosed and at 44 he was diagnosed with diabetes mellitus, currently on oral hypoglycemic agents.
Additionally, he has hypothyroidism and hypertriglyceridemia in management and calcification of the Achilles tendon.
Patient reports he had no child by choice. Patient is product of the union of consanguineous parents second cousins and has a year-old brother with similar clinical characteristics, including voice changes since the age of 28, bilateral cataracts at age 29 subsequently presents complications from corneal ulceration and is currently legally blind , and premature graying since age 33, moreover, scleroderma-like skin changes since his 30s and diagnosis of type 2 diabetes mellitus at age His brother also endorses no child by choice.
No other complications such as atherosclerosis, dyslipidemia, hypertension, osteoporosis, or tumors were reported. There are no other relatives with clinical suspicion of WS.
Patient states maternal aunt has unspecified type leukemia and father with a history of acute myocardial infarction at age 65 and a diagnosis of melanoma at age Maternal uncle diagnosed with lung cancer at age 72 and maternal grandfather with prostate cancer diagnosed at age He had thin upper limbs with decreased subcutaneous fat and truncal obesity Figure 1.
Moreover, we found short stature, hypogenitalism, lower limbs with markedly atrophied skin and subcutaneous fat, abnormal pigmentation of the skin and hyperkeratosis, and flat feet Figures 2 and 3. This variant generates a stop codon at position and has been classified as pathogenic and previously described in homozygous status in a Caucasian patient from the United States in [ 15 ].
EKG showed an elevation of the J point by early repolarization. Abdominopelvic CT-scan showed bilateral renal cysts, small umbilical hernia, and no fatty liver.
Testicular ultrasound showed decreased bilateral testicular volume mainly left side. Regular screening for malignancies is recommended for patients with WS, due to the high risk of early-onset neoplasms. Also, it is very important to rule out cardiovascular and metabolic diseases during the follow-up of these patients. Our patient is still under periodic clinical observation and follow-up. Currently, he is on treatment with oral hypoglycemic agents for DM2 with adequate glucose control and in treatment of hypertriglyceridemia.
Until now no signs of atherosclerosis or cardiovascular disease have been detected. However, he was recently diagnosed with refractory cytopenia with multilineage dysplasia, a form of myelodysplastic syndrome, which has required multiple transfusions.
According to a clinical history, the patient's brother is being monitored for inadequate control of diabetes mellitus and severe skin lesions that have been difficult to treat, but no cancer has been documented. The first clinical sign of WS, often recognized retrospectively, is a lack of the expected pubertal growth spurt leading to relatively short stature on adulthood.
However, sometimes this clinical sign is overlooked and it is usually during early adulthood Patients with WS are normal at birth and have adequate growth and development during childhood. Thereafter, patients begin to progressively develop the typical features of WS such as an aged appearance that includes a bird-like face, gray hair, alopecia, skin atrophy and loss of subcutaneous fat and areas of hypo- and hyperpigmentation. Complications typically beginning in the 30s, such as bilateral cataracts, arteriosclerotic diseases cerebral hemorrhage, cerebral infarction, myocardial infarction, and arteriosclerosis obliterans , hypertension, diabetes mellitus, dyslipidemia, osteoporosis, deep skin ulcer around the ankles, calcification of the Achilles tendon, malignancies, and early loss of infertility associated with gonadal atrophy.
The main causes of death at a median age of 54 years are myocardial infarction secondary to atherosclerosis, diabetes mellitus, and malignant tumors [ 6 ]. WS patients have a much higher incidence of neoplasms and the mean age at first diagnosis of neoplasms is The main features of cancer in WS are early age of onset, high frequency of unusual types, especially sarcomas, and multiple neoplasms [ 17 ]; however common types of cancer have also been described. Cancer risk was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia and the elevated risk of these neoplasms ranges from 8.
We would like to contribute to the literature with our clinical observation of a classic WS case; this patient was diagnosed relatively late because this syndrome was not initially suspected, perhaps because of poor awareness of this rare disease that leads to symptomatic treatment of each manifestation. Although the first clinical sign of WS, often recognized retrospectively, is a lack of the expected pubertal growth spurt, the typical signs of WS appear progressively after puberty.
Therefore, some symptoms may be absent in young patients and this can delay the diagnosis. This demonstrates that knowledge of the early signs of WS and family history can be helpful for early recognition of WS and to establish the diagnosis. Learning Points i WS should be suspected in the presence of cardinal signs, such as voice changes, scleroderma-like skin changes, bilateral cataracts, soft tissue calcification, and appearance of premature aging.
This work is not supported on a grant. The authors declare no conflicts of interest in the manuscript preparation. S1 : WRN gene sequencing report. Description of the methodology and interpretation of the pathogenic variant found. Supplementary Materials. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors.
Read the winning articles. Journal overview. These individuals are also at higher risk for cancer. Most people with this condition die in their late forties. The most frequent causes of death are heart attacks from coronary artery atherosclerosis and cancer. What is the treatment? People with Werner Syndrome are treated for their various symptoms cataracts are removed, heart disease is treated, etc. There is no known cure for the condition. Who gets Werner Syndrome?
Werner Syndrome is a genetic condition. It is caused by a change, or mutation, in the genetic material that is passed on from parents to children. Werner syndrome is estimated to affect 1 in , individuals in the United States.
This syndrome occurs more often in Japan, affecting 1 in 20, to 1 in 40, people. Mutations in the WRN gene cause Werner syndrome. The WRN gene provides instructions for producing the Werner protein, which is thought to perform several tasks related to the maintenance and repair of DNA.
This protein also assists in the process of copying replicating DNA in preparation for cell division. Mutations in the WRN gene often lead to the production of an abnormally short, nonfunctional Werner protein. Research suggests that this shortened protein is not transported to the cell's nucleus , where it normally interacts with DNA.
Evidence also suggests that the altered protein is broken down more quickly in the cell than the normal Werner protein. Researchers do not fully understand how WRN mutations cause the signs and symptoms of Werner syndrome. Cells with an altered Werner protein may divide more slowly or stop dividing earlier than normal, causing growth problems. Also, the altered protein may allow DNA damage to accumulate, which could impair normal cell activities and cause the health problems associated with this condition.
Werner syndrome is inherited in an autosomal recessive pattern , which means both copies of the WRN gene in each cell have mutations.
The parents of an individual with Werner syndrome each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Genetics Home Reference has merged with MedlinePlus. Learn more. The information on this site should not be used as a substitute for professional medical care or advice.
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