Clomipramine

By V. Marik. Athens State College.

The prevalence of previously unrecognized diabetes mellitus or impaired glucose tolerance may be between 20% and 30% [42] buy discount clomipramine 75 mg. There is Body temperature – see Chapter 17 evidence of a positive association between elevated Increased body temperature following stroke has been admission plasma glucose and poor post-stroke out- shown to be associated with poor outcome cheap clomipramine 10mg online. Studies of come buy clomipramine 50 mg amex, with increasing stroke severity clomipramine 25mg discount, higher mortal- anti-pyretic medication and thermal cooling devices ity and reduced functional recovery observed in those have not provided conclusive evidence of efficacy but with hyperglycemia [41, 43]. Tight control of hyper- it is good practice to monitor and treat pyrexia in the glycemia following myocardial infarction and in crit- immediate post-stroke period. A rise in body tem- ically ill patients being managed in intensive care perature can be centrally mediated following stroke, units appears to confer a beneficial outcome, and so but more commonly it suggests the presence of inter- 236 it has been suggested that the same may be true in the current infection. Currently, however, ician to this possibility and, if clinically appropriate, Chapter 16: Acute therapies and interventions such infections should be treated. Paracetamol 1 g can The numbers needed to treat were 2, 4 and 2 respect- be administered every 4–6 hours, to a total dose of ively [47]. Raised body temperature following stroke is com- Intracranial pressure should be maintained at monly treated with antipyretic medication. Early deterioration and death are often due to cerebral edema and rising intracranial pressure, which can occur within 24 hours of stroke, Cerebellar infarction but usually becomes evident between days 2 and 5 Neurosurgical opinion should also be sought in following stroke onset [1]. Medical therapy includes patients with space-occupying posterior fossa infarc- airway management, oxygenation, pain control and tions. Intracranial pressure is not available, expert opinion advises that decom- should be maintained at $70 mmHg and can be pressive surgery and ventriculostomy can be con- lowered by using intravenous mannitol (25–50 g sidered in cases of cerebellar infarction as prognosis every 3–6 hours), glycerol (4 Â 250 ml 10% glycerol can be favorable [1]. Clearly, pressure lowering and reduced hematoma expansion thrombolysis is contraindicated! Graduated compression stockings perfusion pressures in order to maintain adequate have not yet been confirmed to be effective in patients cerebral perfusion. Although the difference surgical intervention (<24 hours) and those who in proportional mean hematoma growth within 6 hours were managed conservatively [51]. This particular subset of patients warrants a larger study to determine the effects on clinical further investigation, which is currently ongoing. For patients with intraventri- Additionally, the recognition by medical and nursing cular hemorrhage, there is some evidence to support staff of stroke as a medical emergency necessitating the use of intraventricular drainage with thrombolytic rapid clinical assessment, diagnosis and treatment agents administered via the catheter to prevent cath- has been essential in maximizing the potential benefit eter obstruction, though trials on this continue [2]. Consequently, trials of its use have been limited to patients without a history of previous Intravenous thrombolysis is a standard therapy for ischemic events. For routine use of alteplase after thromboembolic events were significantly increased stroke there is an upper limit of 3 hours after the in the highest-dose group (160 µg/kg). A further trial onset of stroke, but an extension of this time limit to involving more than 800 patients also found reduced 4. Ten effectively achieved by using a combination of intra- percent of the total dose is administered as an intra- venous vitamin K and prothrombin complex concen- venous bolus with the remaining 90% delivered trate, or fresh frozen plasma. Aspirin and other antiplatelets or anti- coagulants should be avoided for 24 hours following With intracerebral hemorrhage, thrombolysis is thrombolysis. Hypertension should be gradually Transcranial Doppler ‘sonothrombolysis’, micro- lowered. Raised intracranial pressure can be bubble and intra-arterial thrombolysis administration lowered if necessary. In order that patients obtain the full potential benefit of The efficacy of either dipyridamole, clopidogrel, acute stroke therapies, significant changes in the way or a combination of antiplatelet agents has not been stroke services are configured have been required. It is, however, good practice and an appreciation that patients with suspected stroke 239 to commence appropriate secondary prevention should be transported to an appropriate medical Section 4: Therapeutic strategies and neurorehabilitation antiplatelet therapy at the earliest opportunity in Intracranial pressure should be maintained at appropriate patients. A ‘U-shaped’ association between intracranial pressure can be lowered if necessary. Cerebrovasc Dis 2008; acute post-stroke period, the reduction should be 25:457–507. Recommendations for the Management of Measurement of blood glucose is mandatory for Intracranial Haemorrhage – Part 1: Spontaneous all patients with suspected stroke. Intravenous thrombolysis with between elevated admission plasma glucose and poor recombinant tissue plasminogen activator for acute post-stroke outcome, with increasing stroke severity, hemispheric stroke. The National Institute of Neurological Disorders and lowering of hyperglycemia following acute stroke. Tissue plasminogen routine use of insulin infusion regimens to control activator for acute ischaemic stroke. Randomised double-blind placebo Raised body temperature following stroke is controlled trial of thrombolytic therapy with commonly treated with antipyretic medication. Aspirin and clopidogrel compared years with acute ischaemic stroke: Canadian Alteplase with clopidogrel alone after recent ischaemic stroke or for Stroke Effectiveness Study. J Neurol Neurosurg transient ischaemic attack in high-risk patients Psychiatry 2006; 77(7):826–9. Anticoagulants ultrasound monitoring in stroke patients treated with for acute ischaemic stroke.

According to Barthelmes and of the options open to them; however generic 75 mg clomipramine amex, studies Gateley generic clomipramine 10mg amex, 14–44% of pregnancies conceived fnd that fertility issues are not fully discussed after a diagnosis of breast cancer are termi- or that information is lacking1–3 cheap clomipramine 75mg on-line. These numbers suggest the actual per- information is available cheap 75 mg clomipramine fast delivery, women often do not centage of women who conceive after a diag- feel adequately supported in making decisions. Many women success- include lymph node status, tumor size, tumor years) with a pathologically confrmed diagno- younger at the time of their breast cancer diag- fully deliver a healthy child following a diag- grade and hormone receptor status. Various sis of breast cancer, 1421 (56%) had naturally nosis compared to other women aged less than nosis of breast cancer, but still may fear the algorithms can be constructed which then conceived at least one full-term pregnancy 45 years diagnosed with breast cancer, but effects of the breast cancer on the child and/ give a likely prognosis. Further prospective studies are Studies have examined subsequent preg- sive ductal carcinoma, ranging in size from 1 needed, however, to explore how pregnancy nancies in women previously diagnosed with to 90mm, with half less than 20mm in diam- and fertility affect a diagnosis of breast cancer breast cancer. Tables 1 or better survival than similar aged women and 2 show recurrence-free and overall survival who do not conceive after a diagnosis of breast 9,13,18–24 in women who had a subsequent pregnancy Pregnancy is not usually recommended in the cancer. As seen frst 2 years following the treatment of breast a subsequent pregnancy may provide a posi- in the tables, the 5-year overall survival was cancer, as most early recurrences develop tive survival beneft to women. This recommendation is tant, however, to interpret these studies with Recurrence and survival rates were similar not made because the pregnancy will affect caution due to the bias known as the ‘healthy whether survival was measured from time of breast cancer outcome. Moreover, some pregnancy, with four women experiencing vant therapy, available evidence suggests that hormonal agents (including tamoxifen and the more than three subsequent live births. The median time from breast cancer able research examining outcomes and sur- sis of breast cancer, the evidence concerning diagnosis to frst subsequent pregnancy was vival in those who become pregnant and those harms and benefts of this type of contracep- 23 months (interquartile range 11–42). Two research will be necessary to corroborate these Figure 2 Fetal ultrasound tial stimulating effects of progestin is pres- births occurred before 36 weeks: a set of twins fndings. Compared to other women diagnosed with Treatments for early breast cancer in premeno- reasons to explain why women conceive fol- The decision to terminate the pregnancy or breast cancer when they were less than 45 pausal women may include local treatments, lowing a diagnosis of breast cancer. Radiotherapy is it is important that the woman avoids preg- One of the most important issues facing but this result suggests that those women who contraindicated during pregnancy25. Tamoxi- women who have not yet started or completed nancy, and personalized instruction regard- have completed treatment, have good progno- fen has potential fetal toxicity, including Gold- ing the use of adequate mechanical forms of their families when diagnosed with breast sis tumors and are unlikely to have disease enhar’s syndrome12,26. Chemotherapy is likely cancer is fertility preservation and/or options contraception, including condoms or the ft- recurrence during this time can safely consider to be teratogenic in the frst trimester of preg- ting of a diaphragm, becomes a priority. For some women, the opportunity Forty-two (34%) women underwent preg- early stages of development and potential fetal to all pre- and perimenopausal women follow- (rather than the reality) to have a child is more nancy termination. Of the women who ter- damage later on; this is possibly related to the ing their diagnosis of breast cancer for two important than their own long-term survival. Data on the use of Herceptin and Health professionals need to sensitively assess reasons: frst, mechanical contraception is pre- had at least one subsequent live birth. Three pregnancy are very limited, but this agent may ferred, as the oral contraceptive pill is associ- how individuals feel about preserving their main reasons were given for these termina- cause complications, including a decline in the ated with a potentially increased risk of recur- fertility and the importance of maintaining tions: the woman’s fear of disease recurrence; quantity of amniotic fuid28–37. In the frst instance, the recommendation of the clinician; and tion is important in counseling a woman who that chemotherapeutic or hormonal agents any woman of reproductive age should be the woman having received adjuvant therapy may fall pregnant or consider doing so during and radiotherapy may have on a developing offered referral to a fertility specialist for fertil- whilst pregnant. For all women who have had a decline the referral, they should be advised of usually only available to women diagnosed months with an agonist whilst the individual diagnosis of breast cancer, and have endured the impact their breast cancer treatment may with breast cancer who have a male partner is receiving chemotherapy treatment. However, additional discussed prior to and after the completion of who undergo chemotherapy experiencing some needs to be delayed for at least 4 weeks research is necessary to explore the safety and breast cancer treatment47. This has yet the time of their diagnosis, fertility preserving conceive after a diagnosis of breast cancer are pares the number of menopausal women by to be clarifed in research studies, although options are limited, as many options are still fraught with numerous diffculties. Treatments that include therapy with fertility drugs and the retrieval of by reduced ovarian function secondary to treatment with chemotherapy is signifcantly ovarian stimulation, however, may delay the mature oocytes for freezing and later use. For some women this delay in the in relation to the women’s individual cancer poor ovarian function for women diagnosed tions undertaken before chemotherapy com- commencement of treatment is unacceptable. Surgically with breast cancer in their late 30s and early 40s mences can increase the long-term chances Some research fndings indicate that it 5 removing a wedge of ovarian tissue is another makes pregnancy more improbable. Fertility may be useful to preserve a woman’s fertility option where, following cryopreservation, signifcant clinical implications when advising the ovarian tissue can be re-implanted. Use younger women diagnosed with breast cancer of this option has, however, resulted in only who have good prognostic tumors and want 100 a handful of pregnancies worldwide50–53. It 90 With chemotherapy techniques are likely to have increased success is imperative that full counseling concerning Without chemotherapy rates in the future as scientists and clinicians the ramifcations of conceiving and raising a 80 work collaboratively to improve them. Some child following treatment for breast cancer 70 women may not want to receive any fertility be part of the management plan for all young preserving treatment and may wait until after women. In order to make an informed choice about Figure 3 Estimated number of women who become menopausal after chemotherapy depending on their These include oocyte donation, surrogacy her treatment and fertility, it is important age at diagnosis. Anecdotal The obstetric management of a woman who cryopreservation achieving pregnancy legally owned by both partners evidence suggests that impartial and honest conceives after a breast cancer diagnosis should Clinically available Likely to increase circulating estrogen communication from the health professional be the same as for any pregnant woman with levels which may impact on prognosis may help to lower a woman’s distress and a few provisos. Mothers can breastfeed from Ovarian stimulation and Does not require Very few successful pregnancies This latter area may need some improvement, the unaffected breast, although this is very oocyte cryopreservation a male partner Likely to increase circulating estrogen as many women report that they were not unlikely to happen from the affected breast levels which may impact on prognosis fully informed or made aware of the adverse due to the damage caused by radiotherapy. Issues to consider include the type including the cancer surgeons and physicians, Simple to administer Side-effects unknown of interventions available, how effective the and obstetric health professionals should be Unlikely to delay intervention is, potential delays to the cancer used and the pregnancy treated as high risk.

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In a retrospective analysis of still- optimal glycemic control preconception buy 50mg clomipramine free shipping, but should be considered during the preconcep- births occurring in women with type 1 diabe- to have a negative impact on long-term renal tion assessment for all women with longstand- also in preparation for the early weeks of preg- tes best clomipramine 75 mg, a six-fold higher incidence of nephropathy function in women with diabetic nephropathy ing type 1 diabetes and all women with type nancy buy 10mg clomipramine fast delivery. Assessment of renal function creatinine) in contrast to those with low cre- 47 buy cheap clomipramine 10 mg on-line,48 should be considered if other risk factors are Due to the increased frequency of hypogly- with serum creatinine, estimated glomeru- atinine clearance before pregnancy. Prompt return to normogly- be performed in all diabetic women prior to Other complications of diabetes Eating disorders associated with diabetes cemia, after hypoglycemia, may help to reduce conception. Sensorimotor The possibility of disordered eating patterns, between hypoglycemia and congenital mal- neuropathy in women with diabetes rarely including binge eating and insulin restriction formations, but this has not been confrmed causes problems during pregnancy and does 53 to avoid weight gain should be considered dur- in human studies. Autonomic neuropathy is associ- First-line hypoglycemia treatment should be Normal Unknown ated with hypoglycemic unawareness, which Hypoglycemia, usually defned as blood glu- consumption of fast-acting carbohydrates such <30 mg/24 hours can be aggravated by pregnancy. Women need to be aware Once blood glucose levels have recovered, fur- 30–300 mg/24 hours who have developed gastroparesis as a compo- that the tight control required before con- ther hypoglycemia should be avoided by con- Macroalbuminuria Increased pre-eclampsia nent of autonomic neuropathy often have poor ception, and in pregnancy, may predispose sumption of longer-acting carbohydrates such >300 mg/24 hours 49,50 metabolic control and inadequate nutrition. Evers as a cereal bar, fruit, biscuits or the next meal Protein excretion Increased risk of This complication is subsequently associated and colleagues demonstrated that the fre- if it is due. Women should be clearly at the preconception appointment, not least appointment in the antenatal clinic, as each nancy with a general increase as pregnancy informed that if they have high blood sugar because many of these effects can be modifed 1% decrease in preconception HbA1C halves progresses, although this effect varies between levels with ketones, or evidence of urinary by improving diabetic control before concep- the rate of adverse pregnancy outcomes7. There appears to be a triphasic ketones with even moderate blood sugar eleva- tion and maintaining good control throughout Women with long-term diabetes are at pattern of insulin requirements, which remain tions, they should seek medical help urgently the pregnancy. Unfortunately both miscarriage greater risk of developing pre-eclampsia than steady in the frst trimester and increase there- rather than attempting to manage the situa- and fetal anomalies are much more common the background population, and this risk is after55. Unfortunately, since both proteinuria in a prospective study of women with type 1 recognized, and explained to women that both and hypertension are common in pregnan- diabetes, after initial increases in insulin doses Many women with diabetes are not aware that miscarriage and fetal anomalies are not exclu- cies with long-term diabetes, it can be diff- a fall in insulin requirements was observed there is no reason why they should not breast- sive to pregnancies in diabetics, or those with cult differentiating between this phenomenon between 7 and 15 weeks’ gestation56. Unfortunately, changes, in combination with the need to bal- aged, in the interests of both the mother and A comparison of miscarriage rates in 386 these complications cannot be prevented by ance near normal glycemic control with avoid- her baby. Regard- ance of hypoglycemia, result in the need for the preconception appointment and stressed reported a 16% miscarriage rate in both less, there are advantages in discussing these intensive blood glucose monitoring through- throughout antenatal care appointments. Accord- HbA1C level within the normal HbA1C range, in rin (see above), can be considered and poten- Diabetic ketoacidosis ingly, breastfeeding diabetic women should be the above normal range the miscarriage rates tially started early. In a macrosomia, leading to the birth of the clas- more susceptible to diabetic ketoacidosis aware that they can continue taking metformin smaller study of 83 type 1 and type 2 diabetics, sic cherubic infants of diabetics. Kamalakannan and associates reviewed or glibencamide whilst breastfeeding, because 95% of the miscarriages occurred in women they are often unaware that the risk of mac- contributing factors such as increased insu- there is adequate information on the safety of with an HbA level of more than 11. As data including maternal age, duration of diabetes, the pregnancy, especially in the third trimes- which include infection, vomiting and poor on the safety of breastfeeding with the other parity and smoking, and found a relative risk ter. Similarly, a comparison of type 1 dia- restriction can also complicate the pregnan- ops quickly and may be associated with less with these agents before pregnancy are usu- betics with an early pregnancy HbA1C above or cies of women with diabetes and can have marked hyperglycemia than is usual outside ally advised to stay on insulin until they have below 7. It has frequency, risk factors and long-term effects evidence of fetal growth restriction was asso- College of Obstetricians and Gynaecologists long been common practice to advise women of neonatal hypoglycemia, 9. A randomized even with well controlled diabetes delivery have written guidelines for blood sugar man- maternal trauma during delivery with mac- controlled trial of 200 women with insulin- should be considered after 38 weeks (see agement of the neonates of diabetic women8. Both studies found an increase in inevitable as shown by the cesarean section will help the baby maintain its blood glucose enquiry1 reported shoulder dystocia in 7. Neonatal blood glucose testing, pref- of vaginal births in diabetic women, with no cia in the expectant management group, with ing diabetes (40% in 2006 and 42% in 2007). It is thus appropriate to briefy dis- blood glucose level does not improve with less accuracy of estimated fetal weight is worse in Unheralded intrauterine death remains a cuss neonatal management during preconcep- invasive measures8. Neither shoulder dystocia nor in pregnancies complicated by diabetes mel- be reassured that, although the babies of dia- magnesemia, previously unrecognized con- the possible sequelae for the fetus (Erbs palsy) litus. Unfortunately, conventional tests of betic women require careful monitoring and genital heart disease and cardiomyopathy are can always be prevented, but awareness of the fetal well-being are poor at predicting these should therefore be delivered in a unit with all more common in the babies of women possibility and proper and timely management events8. Women may be tor for neonatal hypoglycemia, and, though less of diabetic mothers can be monitored for rare drills for all labor ward staff in its manage- aware of this statistic before they conceive and likely, can still occur in the babies of mothers neonatal complications, and to ensure that the ment. Diabetes in pregnancy: management The effectiveness of glibenclamide in women Developmental toxicity of the angioten- of diabetes and its complications from precon- with gestational diabetes. Pharmacokinetic and pharmacody- 2005;112:710–12 Optimal management of diabetes mellitus is (reissued July 2008) namic advantages of insulin analogues and 30. A Reference Guide to domized trial of active induction of labor and rin for the prevention and treatment of pre- function in nephropathic type 1 diabetic Fetal and Neonatal Risk, 7th edn. For exam- mine agonists, macroprolactinomas (diameter ple, only 11 out of 246 women with a micro- >10mm) may be challenging in this respect prolactinoma displayed asymptomatic tumor progression during pregnancy, and none neces- because of compression and invasion of the sitated surgical intervention owing to tumor surrounding vital structures, recurrence after growth5. Under such Effect of pregnancy on circumstances, it may be advisable for a patient prolactinoma growth with a macroprolactinoma to be operated or irradiated before planning of pregnancy. Prolacti- fetal growth and development nomas tend to enlarge during pregnancy prin- cipally by two mechanisms: (1) loss of shrink- A major concern regarding the management of age effects of dopamine agonists after their a prolactinoma during pregnancy is the safety of withdrawal upon diagnosis of pregnancy; and use of dopamine agonist drugs. The patient women with macroprolactinomas is much ration is highly likely (90%) with use of such cabergoline upon a missed menstrual cycle in more complex, being primarily based on the should then be informed about a small risk agents, most women have been exposed for patients with prolactinoma to make sure that extent and size of the tumor. Since macropro- of tumor enlargement induced by pregnancy- 2–3 weeks when the diagnosis of pregnancy the fetus does not become exposed during the lactinomas tend to be invasive, pregestational associated hormonal changes. As Fewer, albeit more discouraging, data exist to the sellar region or shows a small infrasel- that she should immediately notify her physi- some prolactinomas grow during pregnancy, it regarding the safe use of pergolide in preg- lar extension, then dopamine agonists may be cian if any change in visual acuity or a defect 4 would be advantageous to shrink the tumors nancy.

Familial incidence is the threshold for relatives of patients with multifactorial disorder cheap clomipramine 50 mg with mastercard. Notation for gene locations: this is a shorthand way of describing the position of a gene in the genome order clomipramine 50mg without a prescription. Xq27-28 means that the gene is on the X chromosome purchase clomipramine 10mg on line, on the long arm (p order clomipramine 50mg line, short arm, from French for 885 Each band is assigned a number. The astute observer will have noticed that the example given is that of the fragile site in the fragile X syndrome. A + or – sign before a symbol refer to the addition or absence of whole chromosomes (e. Pairwise concordance: the proportion of pairs of twins concordant for a particular trait. To be more exact: number of twin pairs in which both twins are affected by a condition divided by the total number of twins. Partial trisomy: a translocation occurs where a part of a chromosome becomes attached to a different one. If parents are phenotypically normal carriers of translocations are at risk for having a partial trisomy for the first mentioned chromosome, i. In other words, the proportion of heterozygotes who express (see expressivity) the gene in any degree (some authors see penetrance as an all or none phenomenon, and expressivity as a more variable phenomenon); penetrance is a product of the modifying influence of other genes and the environment; some cases of tuberous sclerosis, for example, have only sparse facial papules because of low penetrance. Pericentric inversion: swapping of chromosomal material from one arm of a single chromosome with the other arm of the same chromosome. When people have 1 copy of a certain allele and share the same phenotype as do people with 2 copies of the same allele the allele is dominant for that trait. A recessive allele would need to occur twice in the same person (2 copies) to be expressed in the phenotype. Co-dominance refers to the situation where the person has 1 copy of the allele and a phenotype that is somewhere between (intermediate) those with 0 and 2 copies of the allele. Philadelphia chromosome: acquired chromosomal abnormality involving a deleted chromosome 22, its long arm being translocated to another autosome, usually chromosome 9; associated with chronic myeloid leukaemia. Pleiotropism (pleiotropic genes): a gene with more than one effect on the phenotype; several genes may contribute to one disorder, and a single gene may contribute to several disorders; many psychiatric disorders may be polygenic, the summation of a number of genes, each of small effect. Polygenes (polygenic): a character that is determined by more than one gene; many genes of small effect acting in concert to produce a phenotype, e. These have demonstrated downregulation of key oligodendrocyte and myelination genes (incl. Polymorphic markers: markers recognising fragments of variable size; at least 2 alleles should be present in the population to be useful. Positional cloning: a set of techniques by means of which disease genes are identified through their position in the genome rather than through their function. Presumed obligate carriers: non-affected relatives the gene or genes for a disorder, such as the mother of a patient with schizophrenia who, although not psychotic herself, has a parent or sibling with schizophrenia. Proband: a sampled individual with a condition or trait; propositus if male, proposita if female. Probandwise concordance: the proportion of co-twins concordant for a trait when ascertained through affected probands; or, number of affected co-twins of an affected proband divided by the total number of twins. If 2 heterozygous parents produce children, there is a 1 in 4 chance of a child being affected: ¼ will be normal, ½ will be carriers or healthy heterozygotes, and ¼ will be affected. In practice, consanguineous matings lead to a slight increase in perinatal mortality rate, congenital abnormalities and learning disorder. The risk is greatly increased if there is a history of recessive disorder in the family. Examples of autosomal recessive disorders include oculocutaneous albinism (ocular albinism is X-linked), congenital goitrous cretinism, Crigler-Najjar syndrome, cystic fibrosis, Friedrich’s ataxia, galactosaemia, Gaucher’s disease, glycogen storage disease, Hurler’s syndrome, Niemann-Pick disease, phenylketonuria, Tay-Sachs disease, and Wilson’s disease. Reciprocal translocation: mutual swopping of part of chromosome between autosomes or between autosomes and sex chromosomes – when this occurs in germ cells the result may be partial trisomies and monosomies; however, the balanced genetic rearrangement may continue on and not be manifest phenotypically unless a gene is disrupted. Recurrence risk: the risk of a relative developing the same condition as an affected probands. Recurrence risk ratio (λ1): ratio of risk of a disorder in a first-degree relative of an affected person/prevalence in general population. When the base rate of a disorder is low a high relative risk is still compatible with a low absolute risk. Ring chromosomes: rare deletion of the 2 ends of a chromosome, the broken ends (telomeres) fusing to form a ring; usually loses some chromosomal material; commonly associated with intellectual disability. This is mainly used for conditions where one gene accounts for much of the variance, which does not include most of the major psychiatric disorders. Sex-linked conditions: There are no proven examples of Y-linked single gene disorders in man.