Late Mortality and Cardiovascular Morbidity After Cancer at a Young Age in Finland

Advances in cancer therapies have led to an improved survival after childhood cancer, but also to numerous late adverse sequelae. We aimed to analyze late cardiovascular effects, the leading non-malignant complications, and mortality after cancer at a young age. Via linkage to the hospital discharge registry, we compared cardiovascular complications among 5-year survivors (13,860) younger than 35 years at cancer diagnosis to those of a healthy sibling cohort. Furthermore, the causes of death and purchases of cardiovascular medications and drugs associated with metabolic syndrome were evaluated after early onset cancer and compared to siblings and the general population by accessing the causes-of-death and the drug purchase registers. Both childhood and young adult cancer survivors were more prone to suffer from all studied cardiovascular conditions than their siblings with the highest hazard ratios (HRs) for cardiomyopathy/ cardiac insufficiency. Standardized mortality ratios (SMRs) were elevated after early onset cancer with respect to overall causes of death, cardiovascular causes, and other causes. Additionally, early onset cancer patients were more likely to purchase drugs for cardiovascular disorders and conditions associated with the metabolic syndrome than siblings. All studied cardiovascular outcomes were highly dependent on the cancer diagnosis and the age at cancer diagnosis. These studies emphasize the need for setting up long-term cardiovascular follow-up guidelines for early onset cancer survivors, especially in young adult cancer survivors who are still at lack of those. The prevention and early detection of cardiovascular late effects is the ultimate goal for their lifelong medical surveillance to ensure them a best possible quality of life.Myöhempi kuolleisuus ja sydän- ja verenkiertoelimistön sairaudet nuoruusiän syövän jälkeen Suomessa Kehittyneiden hoitojen myötä suurin osa lapsuudessa ja nuoruusiässä syöpään sairastuneista selviää taudistaan, mutta heille voi ilmaantua muita terveysongelmia syöpähoitojen myöhäisvaikutuksina. Tämän tutkimuksen tavoitteena oli selvittää sydän- ja verenkiertoelimistön sairauksien ilmaantumista ja kuolleisuutta nuoruusiässä syövän sairastaneilla. Hoitoilmoitusrekisterin (HILMO) avulla analysoitiin alle 35-vuotiaana syöpädiagnoosin saaneiden ja syövästä 5 vuotta selviytyneiden (N=13,860) henkilöiden sydän- ja verenkiertoelimistön sairauksia verrattuna sisaruksiin. Lisäksi verrattiin syöpää sairastaneiden kuolinsyitä sekä heidän kardiovaskulaarilääkkeiden ja metabolisen oireyhtymän lääkkeiden ostomääriä sisarusten ja väestön ostomääriin. Nämä tiedot poimittiin kuolinsyyrekisteristä ja KELAn lääkeostorekisteristä. Lapsuudessa tai nuoruusiässä syöpää sairastaneilla todettiin sisaruksia korkeampi vaara sairastua sydämen ja verenkiertoelimistön sairauksiin. Korkein vaarasuhde koski kardiomyopatiaa/ sydämen vajaatoimintaa. Yli viisi vuotta syövän jälkeen selviytyneiden todettiin menehtyvän ikätovereitaan todennäköisemmin ennenaikaisesti. Syövän lisäksi kuolinsyynä oli verrokkeja useammin sydän- ja verisuonisairaudet. Lisäksi lapsuudessa ja nuoruudessa syövän sairastaneilla todettiin suuremmat vaarasuhteet kardiovaskulaarilääkkeiden ja metabolisen oireyhtymän lääkkeiden ostoihin verrattuna sisaruksiin. Vaarasuhteet tutkimuksen kohteena oleviin sairauksiin olivat selkeästi riippuvaisia syövän diagnoosityypistä ja sairastumisiästä. Tulokset vahvistavat kansainvälistä käsitystä siitä, että nuorena syövän sairastaneet tarvitsevat systemaattisempaa, yksilöllistä ja monesti elinikäistä myöhäisvaikutusseurantaa. Erityisesti nuorena aikuisena syövän sairastaneille ei ole luotu tarkkoja suosituksia siitä, miten myöhäisvaikutusseuranta on syytä toteuttaa. Optimaalisella pitkäaikaisneuvonnalla sydän- ja verenkiertoelinten sairaudet voitaisiin havaita mahdollisimman varhain ja osa sairastavuudesta pystyttäisiin jopa estämään.Siirretty Doriast

Jansen de Vries syndrome : Report of four new patients and review of the literature

Jansen de Vries syndrome (JDVS, OMIM: 617450) is a rare neurodevelopmental disorder associated with hypotonia, behavioral features, high threshold to pain, short stature, ophthalmological abnormalities, dysmorphism and occasionally a structural cardiac condition. It is caused by truncating variants of the last and penultimate exons of PPM1D. So far, 21 patients with JVDS have been reported in the literature. Here, we describe four novel cases of JVDS and review the current literature. Notably, our patients 1, 3 and 4 do not have intellectual disability albeit they have significant developmental difficulties. Thus, the phenotype may span from a classic intellectual disability syndrome to a milder neurodevelopmental disorder. Interestingly, two of our patients have received successful growth hormone treatment. Considering the phenotype of all the known JDVS patients, a cardiological consultation is recommended, as at least 7/25 patients showed a structural cardiac defect. Episodic fever and vomiting may associate with hypoglycemia and may even mimic a metabolic disorder. We also report the first JDVS patient with a mosaic gene defect and a mild neurodevelopmental phenotype.Peer reviewe

Jansen de Vries syndrome:report of four new patients and review of the literature

Abstract Jansen de Vries syndrome (JDVS, OMIM: 617450) is a rare neurodevelopmental disorder associated with hypotonia, behavioral features, high threshold to pain, short stature, ophthalmological abnormalities, dysmorphism and occasionally a structural cardiac condition. It is caused by truncating variants of the last and penultimate exons of PPM1D. So far, 21 patients with JVDS have been reported in the literature. Here, we describe four novel cases of JVDS and review the current literature. Notably, our patients 1, 3 and 4 do not have intellectual disability albeit they have significant developmental difficulties. Thus, the phenotype may span from a classic intellectual disability syndrome to a milder neurodevelopmental disorder. Interestingly, two of our patients have received successful growth hormone treatment. Considering the phenotype of all the known JDVS patients, a cardiological consultation is recommended, as at least 7/25 patients showed a structural cardiac defect. Episodic fever and vomiting may associate with hypoglycemia and may even mimic a metabolic disorder. We also report the first JDVS patient with a mosaic gene defect and a mild neurodevelopmental phenotype

Detection of novel gene variants associated with congenital hypothyroidism in a Finnish patient cohort

Abstract Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH. Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH. Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro. Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH