FAQ - Smith-Lemli-Opitz Syndrome
(Powered by Yahoo! Answers)

anyone know anything about smith lemli opitz syndrome?

does anyone know any support groups for this syndrome please
my friends son is 15 and was diagnosed with opitz as a baby but now has been diagnosed with the above. my friend would like to be in contact with any parents who are dealing with this. she doesnt read or write so that is why i am helping her out. so far we have only been able to find a handful of people in the uk and they all have babies. still hoping and praying for any help. many thanks


If connecting with other parents is your friend's priority, then please connect with the SLOS Network (http://www.med.unc.edu/~hwaage/SLOS/email.html). There are lots of links, a chat room for parents, coping strategies that have worked for other parents of SLOS children, etc. Good luck!


Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomalies/mental retardation (MCA/MR) syndrome caused by a defect in cholesterol synthesis. SLOS is an autosomal recessive genetic condition caused by deficiency of the enzyme 3 beta-hydroxysterol-delta 7-reductase (7-dehydrocholesterol-delta 7-reductase, DHCR7, EC the final enzyme in the sterol synthetic pathway that converts 7-dehydrocholesterol (7DHC) to cholesterol.

Affected individuals usually have low plasma cholesterol levels and invariably have elevated levels of cholesterol precursors, including 7DHC. Severely affected individuals (those with the condition formerly referred to as SLOS type II) have multiple congenital malformations and are often miscarried or stillborn or die in the first weeks of life. Dysmorphic facial features, microcephaly, second- and third-toe syndactyly, other malformations, and MR are typical. Mildly affected individuals may have only subtle dysmorphic features and learning and behavioral disabilities.


The classic paradigm for the pathogenesis of an inborn error of metabolism includes the accumulation of a toxic precursor and/or deficiency of an essential product as a result of an enzyme deficiency. In the case of SLOS, the precursor 7DHC is potentially toxic in large concentrations, and cholesterol deficiency is almost certainly detrimental. David Smith, Luc Lemli, and John Opitz initially described SLOS as a genetic MCA/MR syndrome in 1964. They named the condition RSH after the first initial of the last names of the first 3 patients ascertained. The clinical characteristics of SLOS have been well established over the past 4 decades.

The etiology of SLOS was unknown until 1993 when Irons, Elias, and Tint et al discovered that patients with SLOS had low plasma cholesterol levels and accumulated sterol precursors such as 7DHC. A deficiency of the microsomal enzyme DHCR7, which reduces the 7-8 double bond of 7DHC to form cholesterol in the final step of the cholesterol synthetic pathway, was hypothesized and later proven to cause SLOS. Mutations in the DHCR7 gene are responsible for SLOS. Therefore, SLOS can now be considered a classic inborn error of metabolism.

Currently, the reason defects in cholesterol synthesis cause congenital malformations is not known. Several disparate lines of research have led to recent understanding of the critical and somewhat unexpected role of cholesterol in early human development. Cholesterol is important in cell membranes, serves as the precursor for steroid hormones and bile acids, and is a major component in myelin. Cholesterol is covalently bound to the embryonic signaling protein sonic hedgehog (Shh) in a necessary step of the autoprocessing of the precursor to active form, occurring about age gestational day 0-7 in humans.

Shh plays a critical role in several embryologic fields relevant to SLOS (eg, brain, face, heart, limbs). Therefore, cholesterol is an essential triggering agent in the early developmental program of the human. Because 7DHC can also activate Shh, cholesterol deficiency leading to decreased activation of Shh is probably not the sole explanation for congenital malformations in this syndrome.

Abnormalities in the Shh-patched signaling cascade presumably play a role. Membrane instability and dysmyelination from cholesterol deficiency and accumulation of 7DHC and other potentially toxic cholesterol precursors are also likely to contribute to the SLOS phenotype.


In the US: Prevalence of SLOS has been estimated to be 1 in 20,000-60,000 births among whites. SLOS is also not uncommon in Hispanics. Its specific prevalence in different populations has not been precisely determined yet. The higher-than-expected prevalence of SLOS suggests a heterozygote advantage. Only 1 description of an African American patient has been published, though no biochemical or molecular confirmation of SLOS was available for this patient (Hanissian, 1969). In a study of 150 biochemically diagnosed SLOS patients, only 1 individual was of African descent (Kelley, 1997). In 2000, Yu and colleagues did not detect the mutation among 121 Africans from Sierra Leone. In 2001, Nowaczyk and colleagues reported an IVS8-1G>C (common SLOS mutation) carrier frequency of 1.09% (17/1559) in Canadian whites and 0.79% (4/504) Canadians of African descent; however, no African Canadian patients were identified.

The results of Wright and associates' 2003 study indicate an IVS8-1G>C carrier frequency of 0.73% (10/1378) in African Americans. This predicts the prevalence of SLOS due to IVS8-1G>C homozygosity to be 1 case per 75,061 persons in the African American population. Although the African American carrier frequency of the IVS8-1G>C allele was determined to be 0.73%, few African American patients with SLOS have been identified.

Carrier frequency for SLOS is approximately 1 in 30 persons of northern European descent, suggesting a disease frequency of 1 per 5000-18,000 people. The actual disease prevalence may be lower because of fetal losses.


SLOS has been described in patients from the United States, many northern European countries, Japan, South America, and other countries. SLOS appears to be uncommon in Japan. The frequency of SLOS appears to be similar in northern Europe and the United States, but additional studies are needed to determine the frequency of SLOS in other regions.


Spontaneous abortion of fetuses with SLOS is not unusual. Stillbirths have also been reported. Death from multi-organ system failure during the first weeks of life is typical in individuals with SLOS type II. Congenital heart disease is not uncommon in SLOS and can cause cyanosis or congestive heart failure. Vomiting, feeding difficulties, constipation, toxic megacolon, electrolyte disturbances, and failure to thrive are common and, in some cases, related to gastrointestinal anomalies. Visual loss may occur because of cataracts, optic nerve abnormalities, or other ophthalmologic problems. Hearing loss is fairly common.

Cause of death can include pneumonia, lethal congenital heart defect, or hepatic failure. Survival is unlikely if the plasma cholesterol level is less than approximately 20 mg/dL as measured by gas chromatography, which is used because routine methods of cholesterol measurement include precursor sterols.


As an autosomal recessive genetic condition, SLOS is equally prevalent among males and females.


SLOS is a genetic condition that is present from conception, but signs may occasionally be so subtle that patients avoid detection until later childhood or even adulthood. Some have postulated that the mildest cases may completely escape detection in some instances. More commonly, SLOS is suspected at birth or shortly thereafter because of birth defects.

Medical Care

Currently, no treatment has proven effective for patients with SLOS. Potentially, cholesterol supplementation is a logical treatment because it may be expected to raise plasma and tissue cholesterol levels. By feedback inhibition of hydroxymethylglutaryl-coenzyme-A-reductase, cholesterol supplementation may reduce levels of 7DHC and related cholesterol intermediates that may be toxic. Dosing guidelines, optimal form of cholesterol to be administered, and whether supplemental bile acids are needed are some of the questions remaining in development of therapy. The major question is whether cholesterol supplementation makes a difference. Therapeutic trials are underway.

Cholesterol supplementation leads to increased plasma cholesterol levels and variable decreases in 7DHC. Kelley et al reported anecdotally that cholesterol suspension has allowed some patients to sleep through the night for the first time and others to overcome aberrant behaviors, to learn to walk, to speak for the first time, and to become responsive sociable family members. Well-controlled clinical trials of cholesterol supplementation showing clear clinical benefit have not yet been published.

Doses of cholesterol used in therapeutic trials have varied from 20-300 mg/kg/d; in some studies of treatment in SLOS, supplemental bile acids were incorporated as well.

Pharmacological crystalline cholesterol in oil or aqueous suspension was used in early studies. Other options for cholesterol supplementation include use of egg yolk, whipping cream, and butterfat.

The early promising results of clinical trials in patients with SLOS, the known severity of the untreated condition, and the ability to confirm the diagnosis prenatally have drawn attention toward preconceptional and prenatal therapy.
Fetal therapy, like the therapeutic trials for adults and children, should be recognized to be possibly palliative and not curative. The findings that cholesterol is essential in early embryonic development and that the yolk sac is the source of cholesterol at this time suggest a critical period or therapeutic window in the periconceptional period. Most prenatal diagnoses are made during the second trimester. Cholesterol delivery across the placenta and the blood-brain barrier pose significant future challenges.

Antenatal therapeutic intervention for SLOS was recently reported. Supplementation of cholesterol was provided by fetal intravenous and intraperitoneal transfusions of fresh frozen plasma during the third trimester. Fetal cholesterol levels and fetal red cell mean corpuscular volume rose, which further indicated that the exogenous cholesterol was incorporated into the fetal erythrocytes. Irons et al concluded that antenatal treatment of SLOS by cholesterol supplementation is possible and may be beneficial in elevating cholesterol levels. No positive or negative effects on the baby were obvious postnatally, but follow-up is ongoing. To speculate that the sooner the sterol derangements can be addressed therapeutically the greater the potential decrease in severity is reasonable. Therefore, antenatal therapy may lead to improvement in SLOS clinical expression.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have recently been studied as potential therapy for SLOS. Statins would be expected to lower 7DHC concentrations. Interestingly, in contrast to the effects in healthy individuals, statins do not appear to lower plasma cholesterol levels in many of those with SLOS. Some statins cross the blood-brain barrier. Whether statins will emerge as a useful therapy for SLOS has yet to be determined.

Hormone supplementation may be needed for some patients with SLOS.

Hearing aids may be of great benefit for those with hearing loss.

Gastrostomy feeding may be indicated.

Patients should limit exposure to the sun and use liberal amounts of sunscreen.

Surgical Care:

Consider repair of congenital heart defects in cases of SLOS type I.

Repair of polydactyly is best performed early.

Consider cleft palate repair as well as pyloromyotomy in a timely fashion in cases of pyloric stenosis.

Rectal biopsy for evaluation of ganglion cells may be useful when Hirschsprung disease is suspected and surgical management for Hirschsprung disease may be needed.
Gastrostomy placement, with or without fundoplication, may be necessary when feeding difficulties or gastrointestinal reflux is present.


Medical geneticists and/or metabolic-disease specialists should be consulted.

Depending on the extent of congenital malformations, the following consultations are often needed:

- Pediatric gastroenterologists
- Pediatric surgeons
- Ophthalmologists
- Cardiologists
- Developmental/behavioral pediatricians
- Occupational therapists
- Physical therapists
- Speech/language pathologists
- Audiologists
- Child psychologists and/or psychiatrists
- Pediatric otorhinolaryngologists
- Facial and plastic reconstructive surgeons
- Pediatric urologists


A high-cholesterol diet may be useful (see Medical Care). Cholesterol should not be considered as a specific treatment of SLOS until efficacy is proven in controlled trials.


No medications have been proven effective in treatment of SLOS. Cholesterol given as egg yolk or crystalline cholesterol in oil or aqueous suspension or sprinkled on food has been used in clinical trials with limited success, but these studies are ongoing. Bile acids, including ursodeoxycholic and chenodeoxycholic acids, have been given in addition to cholesterol in some cases.

Exchange transfusions and transfusions of fresh frozen plasma also have been used in clinical trials. Visit ClinicalTrials and Office of Rare Diseases: Research and Clinical Trials for more information regarding clinical trials.

HMG-CoA reductase inhibitors (statins), including simvastatin, are also beginning to be used in clinical trials along with cholesterol supplementation.

Further Inpatient Care

The condition of patients with the most severe type of SLOS, sometimes referred to as SLOS type II, is characterized by very low plasma cholesterol levels (usually, <~20mg/dL [as measured by gas chromatography methods to separate sterols]), obtundation or coma, respiratory failure necessitating mechanical ventilation, and multiple malformations manifesting at birth. This condition is almost invariably lethal. The clinician should strongly consider offering palliative care only.

Further Outpatient Care

Early intervention is often useful. In addition, children affected by SLOS may benefit from receiving follow-up care from a geneticist, metabolic-disease specialist, and/or behavioral/developmental pediatrician familiar with the complications and long-term needs of patients with SLOS.

In/Out Patient Meds:

Supplemental cholesterol may be helpful. Clinical trials are ongoing. Fresh frozen plasma and bile acids have sometimes been administered to patients with SLOS who have very low plasma cholesterol levels or when mildly to moderately affected patients are unable to take their oral cholesterol supplement, often as a result of illness or surgery.


In the newly diagnosed fetus, newborn, or young infant, transfer to a tertiary care academic facility where a medical geneticist or metabolic-disease specialist is immediately available and pediatric general surgeons and appropriate pediatric surgical subspecialists are available may be required. In some cases, the infant may be too ill and unstable to transport.

Transfer or intermittent visits to a facility where active clinical research in SLOS is ongoing may be considered in any age group.


Photosensitivity may occur; instruct patient to avoid prolonged exposure to sunlight and to use sunscreens and clothing judiciously. Supplemental cholesterol, or even fresh frozen plasma (as a source of cholesterol), may be useful in the short term for patients with SLOS who require surgery or who are very ill for any reason. Adrenal insufficiency may occur, and glucocorticoid and/or mineralocorticoid supplementation may be needed.


Many possible complications exist. Virtually every cell in the body is dependent on cholesterol to maintain normal function; therefore, the cholesterol deficiency in patients with SLOS can affect every organ.

Those most severely affected with SLOS are either spontaneously aborted or die in the neonatal period despite maximal therapy.

Many individuals have multiple malformations. Congenital heart disease and brain malformations may be lethal.
Affected individuals who survive may have renal disease, adrenal insufficiency, seizures, failure to thrive, and hepatic dysfunction.


Survival is less likely when the plasma cholesterol level is less than approximately 20 mg/dL as measured by gas chromatography.

Some individuals with SLOS live into adulthood.
Long-term survival may be more common in the era of cholesterol supplementation. Pauli et al reported a 30-year follow-up of 1 of the 3 original patients described by Smith et al. Phenotypic manifestation persisted, though the patient's general health had been excellent. He has severe MR and expresses violent behavioral outbursts. He is medicated for a seizure disorder and behavior control. His diet analysis showed poor cholesterol intake, which was increased dramatically because of possible benefit of dietary cholesterol supplementation. Two months following initiation of this diet, caregivers described him as calmer, happier, and more verbal. Repeat assessment of plasma cholesterol levels did not demonstrate impressive improvement. Although published data concerning long-term prognosis of SLOS patients is scarce, this case report is

Patient Education

The Internet Web site maintained by an SLOS support group, The SLOS Advocacy and Exchange, provides much useful information for families and health care professionals who wish to learn more about the condition or to contact families who also have a child or children with SLOS.

For excellent patient education resources, visit eMedicine's Cholesterol Center. Also, see eMedicine's patient education articles Understanding Your Cholesterol Level.  (+ info)

Information about the genetic disorder Smith Magenis Syndrome is needed please!?

I'm doing a project on the genetic disorder Smith Magenis Syndrome and would like some extra help. I already have quite a few good sites that have information but I'd like some more and I'm having difficulty finding good descriptive ones. Any help would be great!

  (+ info)

What are preventions/treatments/cures for the smith magenis syndrome disease?

Smith-Magenis Syndrome is caused by malformation of chromosome 17, and is not preventable.

This condition occurs in approximately 1 in every 25,000 births.

Various treatments exist :

Administration of Melatonin or Trazadone for sleep disorders.
Administration of Risperdal for violent behavior.
Physical therapy.
Speech therapy.
Occupational therapy.  (+ info)

Smith Magenis Syndrome?

I'm looking for any information about Smith Magenis Syndrome but mainly who is affected by this syndrome. Any help is appreciated!

This is a very rare congenital disorder of chromosomal development. It is not specific to any particular gender or group. If you haven't been diagnosed with it, you are not going to get it now.

Smith-Magenis syndrome - (SMS)

A rare condition that is associated with developmental delay, learning difficulties, behavioral problems and a disturbed sleeping pattern. Ann Smith and colleagues first described this condition in 1982. About 1 in 25,000 children are born with this condition and it is probably under-diagnosed. It is caused by a small deletion (microdeletion) of the short arm of one member of the 17th pair of chromosomes (17p11.2 microdeletion). This deletion can be detected by special diagnostic test called Fluorescent in situ hybridisation (FISH) analysis.

Most children with SMS have developmental delay and moderate to severe learning difficulties. Speech is frequently delayed. The most characteristic features of this syndrome are the behavioral problems. These include several forms of self-injurious behavior such as pulling out fingernails and toenails, wrist biting, hair pulling, skin picking and head banging. There is also a tendency to insert objects into bodily orifices such as the nose and ears. Some affected patients also demonstrate 'self-hugging' and 'lick and flip' (licking their fingers and rapidly flicking the pages of a book) behaviors. Other behavioral problems include aggression, frequent temper tantrums, short attention span and repetitive behavior. Patients with SMS also have a very disturbed sleeping pattern. They appear to require very little sleep and may have an inverted sleep rhythm, staying awake at night and often sleeping during the daytime.

Facial features of SMS are fairly distinctive and include heavy brows, up-slanting eyes, depressed nasal bridge, and a wide mouth with fleshy and averted central portion of the upper lip. Other features include relatively hoarse voice, short fingers, eye problems (such as squint and iris abnormalities), hearing loss (see separate entry, deafness) and spinal curvature (see separate entry, scoliosis). Congenital heart disease and kidney abnormalities are also frequently seen. A high index of suspicion is needed to make this diagnosis. The characteristic behavior and sleep disturbance coupled with the distinctive facial features often suggest the diagnosis, which can be confirmed by FISH analysis to look for the 17p11.2 microdeletion.  (+ info)

disorders and disability, smith magena syndrome?

Smith Magena Syndrome, HELP PLEASE?
My daughter is 16 and has Smith Magena Syndrome and its a mystery to me some of the behaviors she is haveing. I do not know anyone that knows someone that has this syndrome. I am at the point that my head hurts, my heart and I am exhausted. If you can help me click on my avitar and you can e-mail me. Or if you know any information I will be watching for a responce. thank-you. A desperate mom.

You can get more information about smith magenis syndrome at www.prisms.org or at Smith Magenis , PO box 741914, Dallas,Tx 75374 Hope this helps someone out there  (+ info)

how is the smith magenis syndrome inherited?

Smith-Magenis syndrome (SMS) is a relatively rare genetic disorder characterized by a specific pattern of physical, behavioral, and developmental features.

Although SMS is caused by a deletion of genetic material from a portion of chromosome 17, the syndrome usually does not run in families. In most cases, the deletion occurs accidentally at conception when an abnormal sperm or egg from one parent unites with a normal sperm or egg from the other parent. The abnormal sperm or egg contains the missing chromosomal material. These abnormal sperm or eggs are present in everyone; however, the risk of an abnormal conception increases significantly with the parents' ages.

Research has shown a random parental origin of deletion, suggesting that SMS is likely a contiguous gene deletion syndrome. Continguous gene syndromes are conditions that occur as a result of microdeletions or microduplications involving several neighboring genes.

There is no cure for SMS because the disorder is so complex and has received relatively little research attention. Therefore, managing symptoms becomes a priority in those diagnosed with the disorder.Some experts have suggested that every individual with SMS have annual examinations for thyroid function, scoliosis, and eye problems. If any of these tests is abnormal, intervention and further clinical evaluation is appropriate.

Take care always  (+ info)

what is it like to have smith magenis syndrome?

any other information would be greatly appreciated. The project is due April 21

****Go to the website, there's alot more info. there. Good luck with you're project.


Smith-Magenis syndrome (SMS) is a distinct and clinically recognizable genetic disorder characterized by a specific pattern of physical, behavioral, and developmental features. SMS, which was first described in the early 1980's by Ann C.M. Smith, MA (a genetic counselor) and Ellen Magenis, MD (a cutogeneticist), is the result of a deletion of chromosome 17 (17p11.2). The chromosomal deletion occurs from a spontaneous genetic change (mutation) that happens for unknown reasons, therefore, it is not a familial disorder. SMS is considered a rare disorder and is estimated to occur in 1 out of every 25,000 live births. Currently there are over 100 cases reported, however, it is believed that SMS is widely underdiagnosed because clinical features may be subtle. It is expected that with increased awareness, the number of those identified as having SMS will increase.  (+ info)

What is the name of the syndrome that the person may appear to have facial characteristics of down's syndrome?

I previously watched a documentary about sufferers of a syndrome whose facial features appeared to be down's syndrome but it wasn't down's syndrome. The grow to be quite large adults and have special needs. Does anyone know the name of this condition?

Klinefelter syndrome  (+ info)

Are there different types of Down syndrome and what areas of the body does Down syndrome affect? ?

Also, are there any significant statistics related to Down syndrome? Has Down syndrome received any recent attention from the media? Are there any famous people that have Down syndrome.
Answer as many of the above questions as possible.

There are three types of Down syndrome, garden variety Trisomy 21, mosaicism and translocation.

Read more at:

Welcoming Babies with Down Syndrome (English, Spanish, French)

There is a slide show that also incorporates videos of the featured 'More Alike than Different' cast at the National Down Syndrome Congress website:


And great information at the National Down Syndrome Society website:
Down Syndrome Fact Sheet

You might also enjoy

Margaret's Guide to Down Syndrome

For bios of actors with Down syndrome, see:

Down Syndrome and the Acting Gene


DS in Arts and Media


Michael Johnson


Sujeet Desai

Down Syndrome Links at the Family Village website

Check out this recent New York Times article:

The DNA Age: Prenatal Test Puts Down Syndrome in Hard Focus

Have fun with your research!
  (+ info)

What is so bad about having down syndrome?

I think people are a lot colder than they want you to believe. Too many pregnancies prediagnosed with down syndrome are terminated! Doctors tell people that their kid will be like some animal and people believe them. I've met my share of people with down syndrome, and they all seem pretty human to me. On top of that, they were all decent folks, which is a lot more than I can say for the general population. And how does knowing that unborn children are purged because of down syndrome affect those who were born and have down syndrome?

WOW!! I'm so glad that there are other people who's lives have been touched as mine has. See when I was 28 I gave birth to twin girls and one of them was born with Mosaic down syndrome. Of course, I didn't know much about it til now....and yes I was shocked. They are 14 months old now, and such a blessing as well as my two boys. My daughter is about 4 months behind in her milestones, but she is always so happy! Out of all my kids she is the easiest to handle.

It's always nice to have other people, who see that they are more alike, then different from the rest of us.  (+ info)

1  2  3  4  5  

Leave a message about 'Smith-Lemli-Opitz Syndrome'

We do not evaluate or guarantee the accuracy of any content in this site. Click here for the full disclaimer.