Otopalatodigital syndrome

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Otopalatodigital syndrome


Otopalatodigital (OPD) syndrome, also called digitootopalatal syndrome or palatootodigital syndrome, is a rare X-linked genetic disorder that affects bone and facial structure. OPD is fully expressed in males. Females are only mildly affected.


There are two forms of OPD syndrome. Type I is inherited through an X-linked trait with intermediate expression in females while type II is inherited through an X-linked recesssive trait. OPD syndrome type I is also called Taybi syndrome. OPD syndrome type II is alternately called Andre syndrome, cranioorodigital syndrome, or faciopalatoosseous (FPO) syndrome.

A genetic disorder called frontometaphyseal dysplasia , or FMD, has very similar features to type I OPD syndrome.

There are three recognized forms of a genetic disorder called Larsen syndrome : an autosomal dominant type, a recessive type, and a lethal type. All three of these syndromes have similar symptoms to those seen in individuals affected with OPD syndrome. Recent evidence also suggests that Larsen syndrome, recessive type, may in fact be type II OPD syndrome.

As the various names of OPD syndrome suggest, this disorder is characterized by malformations and/or dysfunctions of the ears (-oto-), palate (-palato-), fingers and toes (-digito-), skull (-cranio-), mouth (-oro-), face (facio-), and bones (-osseo-). Some of the characteristics common to both types of OPD syndrome include: a cleft palate, a prominent forehead, a broad nose, widely spaced eyes (hypertelorism), a downward slanting of the opening between the upper and lower eyelids (palpebral fissures), conductive hearing loss, short fingers and toes (brachydactyly ), an abnormal inward curving of the fingers (clinodactyly), a caved in chest at birth (pectus excavatum); short stature (dwarfism), and a congenital dislocation of the elbows caused by a misalignment of the head of the large bone in the forearm (radius).

Genetic profile

Both forms of OPD syndrome are X-linked. The gene mutation responsible for the appearance of type I OPD syndrome has been tentatively assigned to the Xq28 band. It is also believed that type II OPD syndrome is an allelic variant of type I OPD, which is to say that each form of OPD syndrome is caused by different mutations in the same gene or in overlapping genes at the same chromosomal location. Recessive type Larsen syndrome is also believed to be either another allelic variant of OPD syndrome, or identical to type II OPD syndrome. Another extremely rare genetic disorder, Melnick-Needles syndrome also has an overlapping of symptoms with type II OPD syndrome. It is felt that this syndrome is also possibly an allelic variant of OPD syndrome.

OPD syndrome is transmitted via the X chromosome. A female generally possesses two X chromosomes , one from her mother and one from her father. A male generally possesses only a single X chromosome, that from his mother. He gets a Y chromosome from his father. Certain rare exceptions to these inheritance patterns are seen, but in general, a female is an XX and a male is an XY. It is for this reason that X-linked disorders are generally seen in greater numbers of males than females. The male does not possess a second X chromosome that can be expressed. A male either has a mutation on his X chromosome, or he does not. A female, on the other hand, can be either homozygous or heterozygous for an X-linked trait. That is, she can either have two identical copies of this trait (homozygous) or only one copy is this trait (heterozygous).

Type I OPD syndrome is transmitted through a dominant trait. A child of a type I OPD syndrome affected parent has a 50% chance of also being affected with type I OPD syndrome.

Type II OPD syndrome is transmitted through an X-linked recessive trait. A child of a type II OPD syndrome affected parent has a 50% chance of also inheriting the gene for the type II OPD syndrome. Subsequently, if that child is male, he will have expression of the disorder. If it is a female child, then she generally will have milder features. Girls who are homozygous for type II OPD syndrome (inheriting the gene from each parent) will exhibit more severe symptoms than girls who are heterozygous for type II OPD syndrome. Males affected with type II OPD syndrome exhibit symptoms similar to those seen in homozygous girls.


As of early 2001, the incidence of occurrence of both forms of OPD syndrome has not been determined. The lack of occurrence rate data is partially due to the fact that type I OPD syndrome can often have only very mild clinical and radiological symptoms, such that it is often not diagnosed, or even noticed, until type I OPD syndrome is recognized in a more severely affected member of the family.

Type I OPD syndrome is more common than type II OPD syndrome, and as of early 2001, nearly 300 cases had been reported in the medical literature. In 1996, only 25 detailed cases of type II OPD syndrome had been described in the medical literature.

Signs and symptoms

The severity of symptoms experienced by those people affected with OPD syndrome varies widely from practically asymptomatic to symptoms so severe that they cause infantile or prenatal death. In type II OPD syndrome, males are generally affected with far more severe symptoms than females.

There are six abnormalities of the face and head that characterize OPD syndrome: a cleft palate, downwardly slanting openings between the eyelids, widely spaced eyes (hypertelorism), a prominent forehead, a broad nose, and conductive hearing loss.

Conductive hearing loss results from a blockage of the auditory canal or some other dysfunction of the eardrum or one of the three small bones within the ear (the stapes, the malleus, and the incus) that are responsible for collecting sound. In this type of hearing loss, the auditory nerve is normal. In individuals affected with OPD syndrome, complete deafness from birth is often observed. In those individuals with partial hearing, speech disabilities related to this hearing loss are quite common.

In addition to the abnormalities of the head, universal characteristics of OPD syndrome affected individuals also include: abnormally short fingers and toes (brachydactyly); abnormal inward curving of some fingers (clinodactyly); short nails; a congenital dislocation of the elbows, and sometimes the knees; a caved in chest (pectus excavatum) at birth; and, growth retardation.

Symptoms that are characteristic of type I OPD syndrome include: curvature of the spine (scoliosis ); generalized bone malformation, particularly in the bones of the limbs and ribcage; broad distal digits, malformed or missing teeth (hypodontia); and, mild mental retardation.

Symptoms that are characteristic of type II OPD syndrome include: low-set ears, flattened vertebrae in the spine, bowing of the bones of the limbs, flexed overlapping digits, a malformation or complete absence of the large bone in the shin (fibula), malformations of the hips, a small opening in the abdominal wall (hernia) at the navel (omphalocele ), and a malformation of the male genitalia in which the opening of the urethra is located on the underside of the penis, rather than at the tip of the penis (hypospadias).


A diagnosis of OPD syndrome is suggested when a patient presents the five characteristic abnormalities of the head and face accompanied by conductive hearing loss. This diagnosis is confirmed by the observance of brachdactyly and congenital dislocation of the elbows and/or knees.

Type I OPD syndrome is differentially diagnosed from type II OPD syndrome by the appearance of scoliosis. Type II OPD syndrome is differentially diagnosed from type I OPD by the presence of an omphalocele and greater malformations of the bones of the ribcage.

Treatment and management

There are currently no treatments aimed specifically at OPD syndrome. Instead, treatment is on a case-by-case and symptom-by-symptom basis.

Malformations of the head and face can generally be corrected, if necessary, by surgeries. In certain instances, the conductive hearing loss experienced by individuals with OPD syndrome may also be corrected through surgery. When it cannot, hearing aids may be required.

Many of the skeletal abnormalities seen in OPD syndrome affected individuals can either be corrected by surgery or can be alleviated through the use of braces until the bones become more fully developed.

Malformations of the male genitalia and the omphalocele observed in type II OPD syndrome affected infants can also be corrected by surgery.

Certain OPD affected individuals may also benefit from treatments with growth hormone.

In cases of mild mental retardation or speech problems, early intervention programs for these types of developmental delays may also be of benefit.


Most individuals affected with type I OPD syndrome can expect to lead full lives if medical treatments, including corrective surgeries, are sought. Many individuals affected with type II OPD syndrome die either prior to birth or as infants due to respiratory failure associated with the malformation of the bones of the ribcage. If these individuals survive infancy, they also may expect to live full lives after corrective surgeries and other medical treatments.



Alembik, Y., C. Stoll, and J. Messer. "On the phenotypic overlap between severe oto-palato digital type II syndrome and Larsen syndrome. Variable manifestations of a single autosomal dominant gene." Genetic Counseling (1997): 133-7.


Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. [email protected] <http://www.ccakids.com>.

FACES: The National Craniofacial Association. PO Box 11082, Chattanooga, TN 37401. (423) 266-1632 or (800) 332-2373. [email protected] <http://www.faces-cranio.org/>.

Let's Face It (USA) PO Box 29972, Bellingham, WA 98228-1972. (360) 676-7325. [email protected] <http://www.faceit.org/letsfaceit>.

National Foundation for Facial Reconstruction. 317 East 34th St. #901, New York, NY 10016. (800) 422-3223. <http://www.nffr.org>.


"Entry 304120 Cranioorodigital syndrome." OMIM—OnlineMendelian Inheritance in Man.http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?304120>.

"Entry 311300: Otopalatodigital syndrome." OMIM—OnlineMendelian Inheritance in Man.http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?311300>.

"Otopalatodigital (OPD) syndrome I." Jablonski's MultipleCongenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database. <http://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=517>. (February 27, 2001).

"Otopalatodigital (OPD) syndrome II." Jablonski's MultipleCongenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database. <http://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=518>. (February 27, 2001).

"Oto Palato Digital Syndrome Type I and II." NORD—NationalOrganization for Rare Disorders.<http://www.rarediseases.org>.

Paul A. Johnson