Opitz G/BBB syndrome, Opitz syndrome, G
syndrome, BBB syndrome, Opitz BBB/G syndrome, Hypospadias-Dysphagia syndrome,
Opitz-Frias syndrome, Oculogenitolaryngeal syndrome, and
Hypertelorism-Hypospadias syndrome are all names for the same condition. With
this syndrome there can be different manifestations in individuals, even
within the same family.
This genetic syndrome includes a variety of
midline and bilateral anomalies. A genetic syndrome is an hereditary condition
caused by the genes of the family and ancestors of the affected child. It is
not caused by something the mother did, or did not do, while pregnant. When an
individual has a genetic syndrome they have manifestations, or anomalies, that
are similar to other individuals who have the same syndrome. An anomaly is
anything this is differently formed. The degree of involvement among
individuals, even within the same family, can vary greatly.
Opitz G/BBB syndrome is considered
"uncommon." The number of affected individuals is unknown as the
syndrome is not always accurately diagnosed. With careful medical treatment it
is possible for individuals who have Opitz G/BBB syndrome to live long lives.
In 1969 Dr. Opitz and colleagues described two
syndromes. Each was named for the surnames, or last names, of the families in
whom they were first discovered. The G syndrome (G) was described by John
Opitz, Jaime Frias, James Gutenberger, and John Pellet. It was named for one
family whose last name began with the initial G. The BBB syndrome (BBB) was
described by John Opitz, Robert Summitt, and David Smith. In BBB syndrome
(BBB) the three initials stood for three separate families in whom it was
discovered. At that time the two syndromes were believed to be separate
syndromes. Research in 1995
established that the genes which determine this syndrome are located on
both Xp22 (the X chromosome) and on 22q (chromosome 22). This means the
syndrome can either have an X-linked pattern of inheritance on Xp22, or it can
have an autosomal dominant pattern of inheritance on 22q. Only males have the
form on Xp22. In the case of being on 22q both males and females can manifest
and transmit the characteristics to sons and daughters. It was determined
through this research that the two syndromes, once thought to be separate, are
one and the same syndrome with differing manifestations in individuals, even
within the same family. The names G and BBB were combined. Most often now this
condition is called Opitz G/BBB syndrome. The most current research explains
the MID1 gene, and
the MID2 gene.
Ongoing research is working to find a blood test
to determine carriers of the defective gene. The specific genes on the
chromosomes are being mapped. A highly specialized laboratory test is not yet
available, but will be in the near future. At this point the most reliable way
to diagnose Opitz G/BBB syndrome is through a clinical evaluation made by a
highly skilled, board certified geneticist who is familiar with this
particular syndrome. There are other
syndromes associated with the name of Dr. John M. Opitz. They are
different syndromes sharing the name of one busy geneticist.
Opitz G/BBB syndrome includes a variety of
midline and bilateral anomalies, or birth defects. This means that structures
along a midline (an imaginary line going down through the middle of the body)
or two structures which match on each side of the body, can be affected. Most
frequently these include wide-set eyes and other features (hypertelorism), an
abnormal opening in the penis in males (hypospadias), mild to severe
swallowing defects (dysphagia), an abnormality of the anal opening,
undescended testes (cryptorchidism), and a variety of clefts (a fissure, or
split in the lip, palate, uvula, esophagus, larynx or trachea). The fibrous
band of tissue in the brain that interconnects the two hemispheres may never
have formed before birth (agenesis of the corpus callosum, or ACC).
Affected individuals have a distinctive facial
appearance. The head (skull) may be out of proportion or asymmetrical. The
skull may grow slowly. Some have large heads, while others have small heads.
The hairline may come to a point in the front on the forehead ("widow's
peak"). In addition to wide-set eyes and clefts, there may also be skin
folds (epicanthic) on the inside corners of the eyes. The eyes may be crossed
(strabismus). There may be some problems with the tear ducts. The ears may be
small and/or low-set and may be rotated slightly backward. The outside of the
ears (auricles) may be shaped differently. Children with Opitz G/BBB syndrome
often have small ear canals. Often the sinuses are malformed. There may be a
flat nasal bridge. The nose may be wide and may have small and upturned
nostrils. The mouth could have clefts or a thin upper lip. Inside the mouth
there may be a high palate. The bottom of the tongue may be attached too
closely to the gum (short lingual frenum). The teeth may be crowded or have
abnormal placement. Some teeth may be missing. There may be a small chin or
lower jaw.
Individuals who have Opitz G/BBB may have
swallowing difficulties. This is called "dysphagia" and may involve
the voice (larynx), windpipe (trachea), and throat (esophagus) which leads to
the stomach. Many children with dysphagia cannot swallow safely. They may not
use their tongues or chew properly. Food may go into the windpipe instead of
the esophagus. This is called choking, or aspirating. Aspiration can cause
damage to the lungs and pneumonia. It can prevent oxygen from reaching the
brain and may be responsible for mental deficiencies. It is important to
prevent aspirations as death may occur in severely affected infants either at
birth or in early infancy. There may be a small stomach. Some have reflux or
acholasia where stomach contents go back up into the esophagus and then to the
lungs.
Another problem which can also be involved in
the throat is the windpipe, or trachea, itself. Individuals may have what is
called tracheomalacia. The trachea can be "soft" and not able to
hold itself open fully. It can collapse when the individual breathes. The
person may have a wheezing, hoarse, or weak voice. Some individuals sound like
they are snoring. This is called "stridor" and can be mistaken for
asthma. (Individuals who have hypotonia and who also have tracheomalacia need
to use an incredible amount of energy to breathe.) Some have webs connecting
the trachea and esophagus, and some have clefts (openings) of the esophagus
leading into the trachea. Often infants who have Opitz G/BBB are small and
diagnosed as "failure to thrive." They gain weight slowly.
The chest may be caved in (pectus excavatum) or
pointed out (pectus carinatum). The body may have a variety of hernias. There
can be a variety of congenital heart and kidney defects. Skin may be dry and
have some abnormal pigmentation, birthmarks or moles. Boys may have an
abnormal opening in the penis (hypospadias), undescended testes (cryptorchidism)
and chordee. Girls may have abnormal genitalia (splayed labia majora). Both
boys and girls may have a malformation of the anal opening and sometimes
imperforate anus. There may be a deep hole at the tip of the tailbone above
the buttocks (sacral dimple). Often there is constipation.
Some defects of the skeletal/muscular system
include backbone (vertebral) anomalies. Many individuals have a crocked
backbone, a condition called scoliosis. There may be a short neck. The sternum
may be affected. Feet may be flat with crowded toes. Toes and fingers may may
be a different size or shape, be a bent, or "crowded." Hands may
have a single transverse flexion crease in one or both hands. Reduced muscle
tone is common, often referred to as congenital or cerebral hypotonia.
There may be some central nervous system
defects. There may be sensorineural deafness. Mild mental deficiency is seen
in many cases and may be complicated by aspirations due to dysphagia. The
brain can become damaged without oxygen when the individual is aspirating.
Some individuals have seizures; some display some autistic-like behaviors, and
others display inapproriate behaviors. There are often delays in speech and
physical (psychomotor) skills.
The incidence of identical twinning is more
common in the population of diagnosed Opitz G/BBB syndrome than in the general
population.
