Otopalatodigital syndrome Health Article

Definition

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.

Description

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.