Sunday, June 25, 2017

Cri du Chat Syndrome


Cri du Chat syndrome (CdCS) is a genetic condition caused by the deletion of genetic material on the small arm (the “p” arm) of chromosome 5. Alternative names include 5p- syndrome, 5p minus syndrome, and 5p deletion syndrome. It is one of the most common syndromes caused by chromosomal deletion. CdCS is a rare syndrome with an estimated incidence rate of one in 35,000. Named in 1963 by French geneticist Jerome Lejeune, “Cri du Chat” is French for “cry of the cat” and is so named because of the distinctive cry in infancy which resembles the mewing of a cat.

Read more: Cri du Chat Syndrome

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Smith-Magenis Syndrome

awarenesspinSmith-Magenis Syndrome (SMS) is a developmental disorder with patterns of physical, behavioral, and developmental features which occur due to a deletion of chromosome 17. It affects approximately 1:25,000 people, although researchers believe the number is actually closer to 1:15,000. SMS is sometime misdiagnosed as Down syndrome, Fragile X, Williams syndrome, Velocardiofacial syndrome (VCFS), or DiGeorge syndrome, and is one explanation for the discrepancy in the statistics. There are at least 600 diagnosed cases of SMS, the majority of which have been identified in the last few years as a result of more accurate genetic testing. As awareness about this rare syndrome increases, so do the number of diagnoses. Smith-Magenis Syndrome is alternatively known as 17p 11.2 monosomy, 17p syndrome, or chromosome 17p deletion syndrome.


  • Distinct facial features which become more prominent as individual matures: square-shaped face, rosy cheeks, deep-set eyes, flat bridge of nose, mouth turned downward
  • Mild to moderate intellectual disability
  • Delayed speech and language skills
  • Sleep disturbances
  • Behavioral problems: anxiety, aggression, self-injury (such as head banging or skin picking),  self-hugging (which some consider as a unique trait to SMS), compulsive behaviors (such as hand licking and page flipping, or hand squeezing), temper tantrums, hyperactivity, sudden mood shifts
  • Short, broad hands
  • Hoarse voice, hypernasal speech
  • Scoliosis
  • Eye abnormalities resulting in vision problems
  • Reduced sensitivity to pain and temperature
  • Dental abnormalities
  • Distinct broad-step manner of walking
  • Positive behavioral characteristics: affectionate, good sense of humor, excellent long-term memory, charming personalities


Smith-Magenis Syndrome was first identified in 1982 by Ann C. M. Smith, MA, DSc, a genetic counselor and Dr. R. Ellen Magenis, a chromosome expert. SMS is caused by a missing piece of genetic material from chromosome 17, referred to as deletion 17p11.2. The deleted genes encompass approximately 25 genes, including the RAI1 (Retenoic Acid Inducible 1) gene. In 90% of cases SMS is caused by a deletion of RAI1 and in 10% of cases it is caused by a mutation of RAI1. The different sizes of the deletions contribute to phenotypic variation in SMS.

The deletion of genetic material is not usually passed on from parent to child. SMS results from a genetic change that occurs during the formation of reproductive cells or in early fetal development.

Diagnosis & Treatment

As a result of the low number of known patients with SMS, many doctors are not aware of the disorder. A geneticist can perform a chromosome analysis through a blood test. The FISH (Flurorescence In Situ Hybridization) test maps genetic material in a person’s genes and can produce a more accurate detection of SMS. Newly diagnosed patients are also encouraged to undergo screenings for other possible issues with major body systems such as the heart, kidneys, eyes, and skeletal anomalies.

Currently there is no cure for SMS; however, certain types of medication can help with some of the behavioral symptoms. Some parents use psychotropic medications to help stabilize their child’s emotional mood swings, decrease hyperactivity, and reduce anxiety.

Research suggests that the sleep disturbances which cause SMS patients to experience lethargy during the day and restlessness at night, is related to an inverted melatonin cycle. Ingesting the hormone melatonin can sometimes help regulate sleep patterns, which as a result, may also help with other maladaptive behaviors such as aggression and attention problems.


Generally, researchers estimate that individuals with SMS have a normal life expectancy. They can achieve semi-independence with the help of a strong support system from family, school, work, and service providers. The severity of the disorder depends on the size of the genetic deletions. While some patients with SMS experience few symptoms and exhibit few maladaptive behaviors, others have multiple system failures.

New medications provide positive results to improve quality of life. Researchers continue to examine the complexities of the disorder, as well as its relationship to the reciprocal disease of SMS, known as Potocki-Lupski Syndrome (PTLS). SMS results from a deletion of chromosome 17p11.2, whereas PTLS results from a duplication of chromosome 17p11.2.

More Information

Information about SMS is still emerging, but this rare disorder is slowly gaining attention. ABC News did a story about it in 2010 which can be viewed here: SMS: Families Struggle. There are a handful of parents who have a child with SMS who have written about their experiences in online blogs. Take a look at Tales from the Trenches and read about young Garrett who was diagnosed at 18 months. For more information, educational videos, or to connect with other parents and advocates, go to the Parents and Researchers Interested in Smith-Magenis Syndrome (PRISMS) website, the Taylor Bug Kisses Foundation website, or the SMS Research Foundation website.

Parent Category: News

CHARGE Syndrome

ears1CHARGE Syndrome is a genetic disorder with multiple physical, sensory, and behavioral anomalies which occurs in approximately 1 out of every 10,000 births worldwide. Typically, it is caused by mutations in the DNA-binding protein-7 (CHD7) gene. Babies with CHARGE syndrome are born with life-threatening birth defects, including heart defects and breathing problems. Most have hearing loss, vision loss, balance problems, and delays in development and communication.


CHARGE Syndrome was first described in 1979 by Dr. B. D. Hall in a paper on a group of children who had been born with choanal atresia. The term CHARGE was not adapted until 1981 when the most common features of the disorder were established.

CHARGE is an acronym meaning:

Coloboma of the eye
Heart defects
Artesia of the choanae
Retardation of growth and/or development
Genital and/or urinary abnormalities
Ear abnormalities and deafness

Although very few people with CHARGE have 100% of its known features, the term is still used today. In 2005, researchers discovered a mutation in the gene CHD7 on chromosome #8. This gene provides instructions for making a protein that regulates gene activity (expression) by a process known as chromatin remodeling. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. Changes in gene expression during embryonic development likely cause the signs and symptoms of CHARGE.

In most cases, the disorder results from new mutations in the CHD7 gene. The risk of inheriting the mutation from an affected parent is 1 to 2 percent. It affects males and females from all backgrounds and ethnicities.

Symptoms & Behaviors

The most common symptom is ear malformation and it is observed in 90% of patients. The ears are small, low set, protruding, and cup shaped. Deafness or hearing loss occurs in approximately 60% of cases. Presently, CHARGE is the leading genetic cause of deaf-blindness at birth.

The second most common symptom is colobama of the eye. It affects 70 to 80% of patients. It is usually bilateral and affects the posterior segment of the eye.

The third most common symptom is mild to moderate mental retardation. It is observed in 70 to 75% of patients.

Other symptoms can include growth retardation, heart anomalies, genital hypoplasia, low muscle tone, skeletal issues such as neuromuscular scoliosis, and orofacial clefting.

Children with CHARGE show marked delays in motor development. The average age of walking is three to four years. When they are able to walk, it is often with a characteristic gait. Although developmental delays are expected, cognitive impairment is 50% or less.

Behavioral issues of children with CHARGE may include sleep problems, anxiety, withdrawal, self-injurious behavior, OCD tendencies, and inflexible behavior. While some behavioral issues are manageable with medication, research shows that the drugs often lose their effectiveness.


Before the genetic findings and refinement of the criteria, diagnoses were made using solely the CHARGE acronym. Today, a genetic specialist can perform DNA testing to determine if a mutation exists on the CHD7 gene. It is important to note, however, that genetic testing is only successful in two-thirds of cases. No one feature is required to make a diagnosis of CHARGE; diagnosis today is based primarily on a combination of major and minor characteristics and clinical features.

Before CHARGE was recognized, individuals were seen as having a collection of unrelated anomalies and therefore, the treatment they received was uncoordinated. Now, a diagnosis of CHARGE can result in a collaboration by many specialists so that children can receive the help they need to reach their potential.

Other disorders which can look like CHARGE include VATER Association, Retinoic Embryopathy, and Kabuki Syndrome.


Most children with CHARGE have problems in more than one organ system, and typically undergo ten surgeries before the age of 3. Early mortality rates were 10 to 20%, but now with cardiac treatments, survival rates have improved.

While there is no cure for the disorder, children will benefit from physical therapy (gross motor skills), occupational therapy (fine motor skills), speech therapy, and possibly vision and hearing therapy. Early intervention from audiologists and speech-language pathologists can significantly affect functioning level.

It’s important to realize that sensory loss can affect a child’s cognitive ability and behavior. A deficit in hearing or vision may provide difficulties in effective communication, but it is not impossible. Ear problems, for example, can cause balance issues which then affect motor coordination, as well as communication.

Early Intervention programs in many states offer programs to help children from birth to age three at no charge. Click here to learn more about Missouri’s First Steps early intervention program. Contact the Department of Mental Health or your local school district to find out what programs and services are available in your area.

If you are interested in services to help with your child’s hearing or vision loss, contact Missouri’s DeafBlind coordinator or the one in your state.

The Future

As the child grows past developmental stages, the doctor’s visits and therapy sessions will most likely taper off. These children may have a multitude of problems, but they can grow into adulthood and lead healthy and happy lives. Many adults with CHARGE live independently and some are college graduates.

To learn more about CHARGE Syndrome, check out The Charge Syndrome Foundation’s website. 

Parent Category: News

Rett Syndrome

rett_and_mecp2_disorders_quoteRett Syndrome (RTT) is a neurodevelopmental disorder that causes significant developmental regression. It is one of the most physically disabling of the Autism Spectrum Disorders. RTT is rare and is believed to affect 1 in 10,000 females.

First recognized in 1966 by Andreas Rett, RTT was not generally accepted until 1983. In 1999, Dr. Huda Zoghbi located the gene responsible for Rett Syndrome.


RTT is caused by random mutations in the gene MECP2, located on the X chromosome. The MECP2 gene contains instructions for the synthesis of a protein called methyl cytosine binding protein 2 (MeCP2), which is needed for brain development and acts as a biological switch for gene expression. When the MECP2 gene doesn’t function properly and insufficient or abnormal amounts of the protein are produced, it can cause other genes to be abnormally expressed.

Less than 1% of cases are familial, meaning that the faulty gene is rarely inherited. Since the gene is located on an X chromosome, RTT is almost exclusive to females; boys who develop the mutation usually die shortly after birth.


Between six and 18 months of age is when the symptoms usually begin. One of the first symptoms is a slowing of head growth and a loss of muscle tone. Other symptoms include loss of acquired speech and motor skills, repetitive hand wringing or other movements, breathing difficulties (apnea and hyperventilation), seizures (80% have epilepsy), prolonged toe walking, teeth grinding, body rocking, and sleep problems. In most cases, there is a regression in cognition, behavior, social, and motor skills throughout their lifetime. Apraxia, the inability to perform motor functions, is probably the most severely disabling feature, as it interferes with every body movement.

Four Stages of RTT

The first stage is called Early Onset, and usually takes place in the six to 18 month age range. Symptoms, such as a delay in gross motor skills, may be vague and therefore the diagnosis is often overlooked. This stage usually lasts a few months but can extend to over a year.

The second stage is called Rapid Destructive. This usually occurs in the one to four year age range. Symptoms include slowed head growth, loss of social interaction and communication, loss of purposeful hand skills, and irregular breathing.

The third stage is the Plateau stage. This stage usually occurs in females aged two to ten years. The majority of those affected with RTT remain in this stage. Symptoms can include apraxia, seizures, and severe motor problems. In some cases, communication skills may improve in this stage.

The fourth stage is called Late Motor Deterioration. This stage can last for years or even decades. Symptoms include reduced mobility, scoliosis, and muscle weakness.

Diagnosis & Testing

There is currently no cure for Rett Syndrome; however, there are treatments available to help improve the quality of life of the individual, such as physical therapy, speech therapy, and occupational therapy. Genetic testing can confirm a diagnosis in approximately 80% of cases.

Researchers are currently exploring how bone marrow transplants might affect symptoms of RTT.

Little is known about long-term prognosis and life expectancy. Most individuals with RTT survive into adulthood but are wheelchair bound. They often rely on feeding tubes, are unable to communicate, and require round-the-clock care.

For more information, check out the International Rett Syndrome Foundation or the Rett Syndrome Research Trust. To learn more about RTT from a parent's perspective, check out the blog My Silent Angel's Fight.

For a more visual experience, check out the video library at Rett TV.

Parent Category: News

Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, or mental retardation. FXS occurs when there is a mutation in the FMR1 gene. This gene normally produces a protein the body needs for the brain to develop. The change in the gene causes the body to produce only a little of the protein or none at all, which is what causes the symptoms of Fragile X.

According to the CDC, Fragile X occurs in 1 out of every 4,000 boys and 1 out of 6,000 to 8,000 girls.


Fragile X is passed down from parents to their children. Even if the parents do not have the syndrome, they can have children who do have it. When parents do have it, the mutations in their children can be more serious.

The FMR1 gene is found on the X chromosome. Males and females have at least one X chromosome, so both a mother and a father can pass on the mutated gene to their children. A father with the altered gene will only pass the mutation to his daughters, as Y chromosomes produce only sons. Daughters of men who are carriers will likely be normal; however, they risk having children affected by FXS. A mother can only produce X chromosomes, so she may pass it to her sons or daughters.

The mother of a child with an FMR1 mutation is almost always a carrier of a pre-mutation or a full mutation. The FMR1 altered gene can be passed without symptoms and many people are unaware they have it. A pre-mutation (does not have the syndrome but might have Fragile X- associated disorders) form can be passed without anyone showing any signs or symptoms; however, with each generation, the chances increase for the pre-mutated gene to expand and become a mutated gene, which will increase the symptoms. Note that the severity of symptoms in one child does not mean other children will have more or less severe symptoms.

Signs & Symptoms

The signs and symptoms vary, so it’s very hard to diagnose. The mean age at diagnosis is 32 months. There may be developmental delays in crawling or walking, hyperactive behavior, hand clapping or hand biting. Adults with FXS may have problems with tremors or coordination, while women may experience premature menopause or have difficulty in becoming pregnant.

There are certain patterns:

  1. Intelligence: males have an average IQ of 40; females may have a normal IQ but may demonstrate learning disabilities in academics.
  2. Physical: longer face or jaw, large ears, loose, flexible joints, flat feet, low muscle tone. Some physical symptoms may be present at birth, while others may not develop until after puberty.
  3. Social & Emotional: social anxiety, lack of eye contact, fast, choppy speech, easily upset and distressed by unexpected changes in routine, self-injurious behaviors. Hormonal changes can increase symptoms. According to the National Institutes of Health, one-third of males demonstrate aggressive behavior.
  4. Speech & Language: mild stuttering, language delay and may not speak until two or three years of age. Males may repeat themselves, have trouble in expressing themselves or understanding facial clues such as tone of voice and body language. Females usually have average vocabulary and grammar skills, but their social anxiety and shyness may prevent them from communicating well.
  5. Sensory: hypersensitive to sensory stimuli such as certain sounds and textures, and problems with balance and coordination.

Disorders Associated with Fragile X

Autism: Present in about 30% of people with Fragile X. Most males and one-third of females demonstrate Autism-like features such as flapping hands and repetitive actions.

ADHD/ADD: Almost 90% of males and 45% of females with Fragile X also have ADHD or ADD.

Seizures: Approximately 20% experience seizures.

Pervasive Developmental Disorder – Not Otherwise Specified: About 20 to 30% of people with Fragile X also have PDD-NOS.


There is no cure for Fragile X. There is also no definitive, single treatment for its’ symptoms. There are a variety of therapies and medications which are often used to minimize symptoms.
Recently, the drug trial for arbaclofen came to an end which has caused outrage among some parents who saw positive results in their children who were taking the medication. Research continues to help find a therapy or medication which will help lessen the effects of Fragile X. One of the problems in finding a drug to help with the effects is that the symptoms and behaviors vary widely among individuals with FXS.

Early intervention is very important. A child’s brain is still forming, so a child is more capable of learning. It is recommended that any child who presents with developmental delay, borderline intellectual disabilities, or has a diagnosis of autism, should undergo molecular testing for FXS. Even if a child hasn’t been diagnosed with FXS, he/she may be eligible for services.


Genetic testing is used to diagnose this disease. It was reported in a February 2003 issue of Pediatrics that of those surveyed, 24% of families with a child who was diagnosed with Fragile X, had seen a health care provider ten times before Fragile X testing was performed.

There are three types of tests currently used to diagnose FXS:

  1. DNA molecular test [Southern Blot, and Polymerase Chain Reaction (PCR)]
  2. Chromosome test
  3. Protein test


Genetic counseling is recommended for all families who are affected or at risk of having a pre-mutation or an offspring with a full mutation. Genetic counseling can provide information regarding the inheritance pattern. Prenatal testing can be performed by amniocentesis or CVS to determine if a fetus has inherited the gene.

In 1991, researchers funded by the National Institute of Child Health & Human Development (NICHD) discovered the gene that causes Fragile X. Scientists continue to work on treatment and prevention.

There are nearly 30 Fragile X Clinics located across the country which provide those affected by FXS an evaluation and recommendations for treatment. They also provide medical services and therapies. To learn more about the Missouri clinic, visit the University of Kansas Medical Center's website

Molecular DNA testing is offered in Missouri both at the Cardinal Glennon Children's Hospital in St. Louis and at the Autism Center at the University of Missouri Health Care Children's Hospital in Columbia.


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