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Baller Gerold Syndrome

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Synonyms of Baller Gerold Syndrome

Disorder Subdivisions

General Discussion

Baller-Gerold Syndrome is a rare genetic disorder that is apparent at birth (congenital). The disorder is characterized by distinctive malformations of the skull and facial (craniofacial) area and bones of the forearms and hands.

In infants with Baller-Gerold Syndrome, there is premature fusion of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis). As a result, the head may appear unusually short and wide and/or pointed at the top (turribrachycephaly) or relatively triangular in shape (trigonocephaly). Affected infants may also have a prominent forehead; downslanting eyelid folds (palpebral fissures), small, malformed (dysplastic), low-set ears, and/or other craniofacial abnormalities. Baller-Gerold Syndrome is also characterized by underdevelopment (hypoplasia) or absence (aplasia) of the bone on the thumb side of the forearms (radii). In addition, the bone on the "pinky" side of the forearms (ulnae) is unusually short and curved and the thumbs may be underdeveloped or absent. In some cases, additional physical abnormalities and/or mental retardation may also be present. Baller-Gerold Syndrome is thought to be inherited as an autosomal recessive trait.

Symptoms

Patients with Baller-Gerold syndrome are born with premature closure of the joints or seams (sutures) of the skull causing an upward growth of the head giving it a pointed or cone-shaped appearance. The large bone of the forearm on the opposite side of the thumb (ulnar) is short and curved and the short bone of the forearm on the thumb side (radius) is underdeveloped or missing.

Most patients with Baller-Gerold syndrome are very short and have a nasal bridge that is high. They also have a prominent lower jaw.

Hearing loss, absent or underdeveloped thumbs and bones of the hand, abnormalities of the pelvis and spine, a vertical fold of skin over the inner corner of the eye (epicanthal folds), eyes that are set close together, small abnormally developed ears, skin that sheds and/or mental or motor delay may also be present.

Problems with fine motor skills may be present due to the deformities of the hands and arms.

Causes

Baller-Gerold syndrome is caused, in most cases, by a malfunctioning (mutated) gene that has been tracked to a particular site on chromosome 8 known as 8q24.3. Some cases of BGS are the result of an unexpected, spontaneous mutation the cause of which cannot be attributed to the parental transmission (sporadic). In all cases the trait is transmitted by an autosomal recessive inheritance pattern. The responsible gene on chromosome 8 is known as the RECQL4 gene.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, 'chromosome 8q24.3" refers to band 24.3 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Parents of some individuals with Baller-Gerold Syndrome have been closely related by blood (consanguineous). There is at least one report of a child with many of the features of BGS due to the inhalation of sodium valproate, an anti-convulsive medication sometimes used to control epileptic seizures.

Affected Populations

There are too few cases of Baller-Gerold syndrome reported to determine, with any assurance, whether any bias in favor of one gender or another or any preference with regard to ethnicity exists. It is likely that there are between 20 and 30 reported cases.

Related Disorders

Symptoms of the following disorders can be similar to those of Baller-Gerold Syndrome. Comparisons may be useful for a differential diagnosis:

Apert syndrome, also known as Acrocephalosyndactyly Type III, is a rare disorder characterized by premature closing of the joints or seams (sutures) of the skull causing the head to be pointed (craniosynostosis), a flattened nasal bridge, eyes that are set wide apart, a high palate, fingers and toes that are fused or webbed, vertebral and wrist deformities and/or mental retardation. This disorder is inherited as an autosomal dominant trait. (For more information on this disorder, choose "Apert Syndrome" as your search term in the Rare Disease Database.)

Carpenter syndrome, also known as Acrocephalopolysyndactyly, is a rare disorder characterized by premature closing of the joints or seams (sutures) of the skull causing the head to be pointed (craniosynostosis), abnormally short fingers that are webbed, more than five toes on each foot, skin abnormalities and possible mental retardation. (For more information on this disorder, choose "Carpenter Syndrome" as your search term in the Rare Disease Database.)

Crouzon disease is a rare disorder inherited as an autosomal dominant trait. This disorder is characterized by premature fusion or closure of the skull (craniosynostosis), an unusually wide distance between the eyes, a condition in which the eyes do not look in the same direction, and protrusion of the eyeballs. Swelling of the optic disk inside the eye and optic atrophy may develop. Impaired vision and/or hearing loss may be present in some cases. Dental malformations, an underdeveloped upper jaw, a beak shaped nose, and/or a high palate may also be present. (For more information on this disorder, choose "Crouzon Disease" as your search term in the Rare Disease Database.)

The following disorders are sufficiently similar to Baller-Gerold syndrome that a diagnosis was made, in each case, in error for BGS.

RAPADILINO syndrome
RAPADILINO syndrome is a vary rare, autosomal recessive disorder, the acronym of which stands for: RAdial hypo-/aplasia (underdeveloped bones of the forearm), PAtellae hypo-/aplasia (underdeveloped knee-caps) and cleft or highly arched PAlate, DIarrhoea and DIslocated joints, LIttle size (short stature: < 2SD) and LImb malformation, and NOrmal intelligence.

As of 2003 there were only 17 cases of RAPADILINO syndrome reported in the medical literature. Of these, 14 came from families in Finland. The cause of RAPADILINO syndrome is attributed to one or more mutations in the RECQL gene, as is the cause of Baller-Gerold syndrome.

Roberts syndrome
Roberts syndrome and BGS share several symptoms that have caused confusion in the past. In addition to short stature and low birth weight, in each case the arms are shorter than normal and cleft lip and cleft palate are present. Head shapes and facial features are similar as well. In each case inheritance is as an autosomal recessive trait, and in each case parental consanguinity has contributed to the occurrence in siblings. (For more information on this disorder, choose "Roberts syndrome" as your search term in the Rare Disease Database.)

Rothmund-Thomson syndrome
Rothmund-Thomson Syndrome is an extremely rare inherited multisystem disorder that is usually apparent during early infancy. The disorder is typically characterized by distinctive abnormalities of the skin, short stature and other skeletal abnormalities, malformations of the head and facial (craniofacial) area, and other physical abnormalities, defects of the hair, and clouding of the lenses of the eyes (juvenile cataracts). In rare cases, mental retardation may be present. The range and severity of symptoms may vary from case to case. (For more information on this disorder, choose "Rothmund-Thomson syndrome" as your search term in the Rare Disease Database.)

Saethre-Chotzen syndrome
In many infants with Saethre-Chotzen syndrome, cranial sutures may fuse unevenly, causing the head and face to appear somewhat dissimilar from one side to the other (craniofacial asymmetry). Additional malformations of the skull and facial (craniofacial) region may also be present, such as widely spaced eyes (ocular hypertelorism) with unusually shallow eye cavities (orbits), drooping of the upper eyelids (ptosis), and abnormal deviation of one eye in relation to the other (strabismus). Some affected individuals may also have a "beaked" nose; deviation of the partition that separates the nostrils (deviated nasal septum), small, low-set, malformed ears; and an underdeveloped upper jaw (hypoplastic maxilla), The disorder is also associated with malformations of the hands and feet, such as partial fusion of soft tissues (cutaneous syndactyly) of certain fingers and toes (digits), unusually short digits (brachydactyly); and broad great toes. Although intelligence is usually normal, some affected individuals may have mild to moderate mental retardation. Saethre-Chotzen syndrome is usually inherited as an autosomal dominant trait.

VACTERL
VACTERL association is a nonrandom association of birth defects that affects multiple organ systems. The term VACTERL is an acronym with each letter representing the first letter of one of the more common findings seen in affected children:

(V) = vertebral abnormalities
(A) = anal atresia
(C) = cardiac (heart) defects
(T) = tracheoesophageal fistula
(E) = esophageal atresia
(R) = renal (kidney) abnormalities
(L) = limb abnormalities

In addition, to the above mentioned features, affected children may also exhibit less frequent abnormalities including growth deficiencies and failure to gain weight and grow at the expected rate (failure to thrive). In some cases, the acronym VATER association is used. Mental functioning and intelligence is usually unaffected. The exact cause of VACTERL association is unknown. Most cases occur randomly, for no apparent reason (sporadic). (For more information on this disorder, choose "VACTERL Association" as your search term in the Rare Disease Database.)

Standard Therapies

Treatment of Baller-Gerold syndrome involves surgery to relieve pressure inside the skull due to the craniosynostosis. This can be done by separating the bony sections and lining the seams between them with materials to prevent fusion. The younger the patient is at the time of the surgery the better the results.

Surgery to correct other skeletal deformities may be required and physical as well as occupational therapy may also help in the development of fine motor skills.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources contact:
www.centerwatch.com.

Baller Gerold Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Temple IK. Baller-Gerold Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:157-58.

Gorlin RJ, Cohen MMJr, Hennekam RCM. Eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:674.

Jones KL. Ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:430-31.

Castriota-Scanderberg A, Dallapiccola B. Abnormal Skeletal Phenotypes. Springer Verlag. Berlin, Germany. 2005:28, 381.

Stevenson RE, Hall JG. Human Malformations and Related Anomalies. 2nd ed. Oxford University Press, New York, NY. 2006:224.

JOURNAL ARTICLES
Kellermayer R. The versatile RECQL4. Genet Med. 2006;8:213-16.

Larizza L, Magnani I, Roversi G. Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping. Cancer Lett. 2006;232:107-20.

Van Maldergem L. Siitonen HA, Jalkh N, Chouery E, et al. Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene. J Med Genet. 2006;43:148-52.

Seto ML, Lee SJ, Sze RW, Cunningham ML. Another TWIST on Baller-Gerold syndrome. Am J Med Genet. 2001;104:323-30.

Megarbane A, Melki I, Souraty N, Gerbaka J, et al. Overlap between Baller-Gerold and Rothmund-Thomson syndrome. Clin Dysmorphol. 2000;9:303-05.

Quarrell OW, Maltby EL, Harrison CJ. Baller-Gerold syndrome and Fanconi anaemia. Am J Med Genet. 75:228-9.

Cohen MM Jr. Toriello HV. Is there a Baller-Gerold syndrome? Am J Med Genet. 1996;61:63-4.

Huson SM, Rodgers CS, Hall CM, Winter RM. The Baller-Gerold syndrome: phenotypic and cytogenic overlap with Roberts syndrome. J Med Genet. 1990;27:371-75.

FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Baller-Gerold Syndrome. Entry Number; 218600: Last Edit Date; 10/6/2006.

Baller-Gerold syndrome (BGS). Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. nd. 2pp.
www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=46
Accessed 10/30/2006

Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 218600; 2/14/99. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?218600.

Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:430-431.

Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:469.

Report last updated: 2007/08/17 00:00:00 GMT+0