Rubinstein-Taybi syndrome

Definition

Rubinstein-Taybi syndrome is a rare genetic disorder involving mental retardation, short stature, broad thumbs and great toes, and characteristic facial features. First described in 1963 by the American physicians Dr. Jack Rubinstein and Dr. Hooshang Taybi, over 550 cases have since been reported.

Description

The clinical picture of Rubinstein-Taybi syndrome (RSTS) is highly variable. The most prominent features include mental retardation, thumb and great toe abnormalities, and distinct facial characteristics.

Rubinstein-Taybi syndrome may also be referred to as broad-thumb-hallux syndrome or Rubinstein syndrome. The abbreviation for Rubinstein-Taybi syndrome is denoted "RSTS" or "RTS," although "RSTS" is preferred so as not to be confused with other syndromes such as Rett syndrome and Rothmund-Thompson syndrome.

Genetic profile

A change in a particular gene , known as the CREB binding protein (CBP) gene, causes RSTS. This gene is located on chromosome 16. Its position is denoted as 16p13.3 where p represents the short arm of the chromosome and 13.3 indicates the exact location on the arm.

CBP codes for a protein known as the human cyclic AMP regulated enhancer binding protein (CREBBP). CREBBP has many functions within a cell. Its general role is to regulate multiple pathways and the work of other genes. It is thought that this multifunctional aspect of CREBBP is what causes the diffuse abnormalities observed in RSTS.

RSTS is thought to be autosomal dominant. Only one copy of the CBP gene must be changed or mutated for a person to have RSTS. Most cases of RSTS are sporadic. That is, the majority of affected individuals do not have a parent with RSTS, rather RSTS arose due to a new mutation in the CBP gene. Sporadic mutations in genes occur by chance. They are rare and there is nothing a person can do during a pregnancy to cause or prevent them.

Demographics

The incidence of RSTS has been estimated at between one in 125,000 and one in 300,000 live births. Males and females are affected equally. Cases of RSTS have been observed throughout the world. Although RSTS is thought to be a rare disease, more cases are being diagnosed each year. In part, this is thought to be due to physicians' increasing awareness of the signs and symptoms involved in RSTS.

Signs and symptoms

RSTS is a genetic disorder involving primarily physical malformations and mental retardation.

Babies with RSTS may be born small compared to other newborns. They often have trouble feeding and may need to be assisted in this area. In conjunction with feeding problems, there may be respiratory (breathing) difficulties.

As the child matures, growth remains delayed, with short stature persistent throughout life. An average height of 60 in (153 cm) in males and 58 in (147 cm) in females and an average weight of 106 lb (48 kg) in males and 120 lb (55 kg) in females has been reported.

Developmental milestones are usually delayed. Although most children with RSTS learn to walk and talk, they tend to develop these skills much later than their peers. For example, the average age at which children with RSTS learn to walk is 30 months, compared to 12 months in unaffected children.

There are several unique physical characteristics associated with RSTS. Typical facial features include down-slanting eyes, beaked nose, and the fleshy septum of the nose extending beyond the nostrils. By two to three years of age, most affected children grow into what is considered the classic physical picture of RSTS. Because of their similar facial appearances, they may resemble other children with RSTS as much as or more than they resemble family members.

The most well known features of patients with RSTS are the broad thumbs and great toes (halluces). This finding may be observed at birth although some patients with RSTS have only broad thumbs, only broad toes, or neither.

Other findings that occur on a less frequent basis include malignant (cancerous) and benign (non-cancerous) tumors, chronic ear infections, early onset of breast development in females, kidney abnormalities, high arched palate (roof of the mouth), malformed teeth (named talon cusps after their shape), heart defects, small head, and short upper lip with a pouting bottom lip.

Mental retardation of varying degrees is a constant in RSTS. Affected individuals may present mild to severe mental retardation. They have particular difficulty in expression through speech. Although affected individuals are usually able to understand what is spoken to them, they have a difficult time responding with spoken words. In general, it has been observed that many patients with RSTS do not progress beyond a first-grade level.

It has been noted that affected individuals tend to have happy, outgoing, and energetic personalities. They have been described as people who "know no strangers." People with RSTS tend to smile often, although, due to their physical differences, this smile is sometimes described as a grimace.

Not every person with RSTS will have all of the aforementioned medical, physical, and social characteristics. Although people with RSTS have much in common, it is important to remember that each person is unique with his or her own qualities and challenges.

Diagnosis

Diagnosis is usually based on clinical findings. Laboratory techniques for definitive diagnosis by DNA analysis are available, but at this time are only able to identify approximately 25% of affected individuals. This is due to the considerable number of different changes within the same gene that all may lead to RSTS.

Prenatal diagnosis is available for RSTS; however, again, only approximately 25% of cases are picked up by current available techniques. Because the physical features associated with RSTS are difficult to distinguish prenatally, and the available DNA test does not identify most cases, the vast majority of individuals with RSTS are diagnosed after birth.

The age at which a person is diagnosed varies from patient to patient due to the range in severity of clinical findings. Those with a more mild presentation tend to be diagnosed later in life. Diagnosis may be more difficult in non-Caucasian persons due to the great majority of research and published data having been done on Caucasian patients.

Studies have been conducted in an effort to better identify individuals with RSTS. In 2000, the outcome of a study aimed at improving laboratory techniques for RSTS diagnosis was published. The data suggested that it soon may be possible to identify more affected individuals by DNA analysis both prenatally (before birth) and postnatally (after birth).

Misdiagnosis is sometimes made between RSTS and Saethre-Chotzen syndrome because of their similar clinical findings.

A correct diagnosis is important when providing a family with genetic counseling . A family with a child with RSTS can have many questions. Genetic counseling may be helpful in providing the family with some answers, including information about the risk of having another child with RSTS.

In general, a recurrence risk of 0.1% is given to couples that have had one child with RSTS. For individuals with RSTS there is 50% chance of passing the condition on in each pregnancy.

Treatment and management

Treatment and management is aimed at encouraging and supporting cognitive development and alleviating medical symptoms. There is no cure for Rubinstein-Taybi syndrome.

Medical problems, such as ear and respiratory infections, are treated as they occur. Chronic ear infections may lead to hearing loss and it is therefore important to have this infection treated as quickly as possible.

Early intervention and occupational and physical therapy are encouraged along with behavioral management. It has been shown that children with mental retardation and developmental delay, due to any cause, benefit from these therapies. In particular, for children with RSTS, speech therapy and alternate forms of communication, such as sign language, have been found to be helpful. Alternative avenues of communication may help children with RSTS express their thoughts and feelings and reduce the frustration they may feel at not being understood verbally.

Prognosis

Prognosis is variable due to the wide range of presentations among affected individuals. Mental retardation and developmental delay may range from mild to severe, with a reported average IQ of 51 (the general population average IQ is 100). Medical problems also vary in number and severity.

Most individuals with RSTS will have a normal life span. As adults, affected individuals may live in group homes or supervised apartments. Many work in sheltered workshops or in supervised employment situations.

Individuals with RSTS are capable of having children of their own. In a study of 502 individuals with RSTS, two had reproduced. In total they had three children, one affected with RSTS and two unaffected. It has also been the case that a very mildly affected woman was not diagnosed with RSTS until her child was born with the same disorder.

Resources

PERIODICALS

Baxter, Garry, and John Beer. "Rubinstein-Taybi Syndrome." Psychological Reports 70, no. 2 (April 1992): 451–56.

ORGANIZATIONS

Rubinstein-Taybi Parent Support Group. c/o Lorrie Baxter, PO Box 146, Smith Center, KS 66967. (888) 447-2989. lbaxter@ruraltelnet. <http://www.specialfriends.org>.

WEBSITES

Online Rubinstein-Taybi Pamphlet. <http://www.rubinstein-taybi.org/html/pamplet.html>.

Rubinstein-Taybi Website. <http://www.rubinstein-taybi.org>.

The Arc—A National Organization on Mental Retardation. <http://www.thearc.org>.

Java O. Solis, MS