Desbuquois syndrome

Desbuquois syndrome (DBQD) is a rare type of osteochondrodysplasia (a disorder of the development of bones and cartilage). Characteristics may vary in severity and can include short stature with short extremities, severe joint laxity with dislocation, osteopenia, kyphoscoliosis, distinctive facial characteristics and other abnormalities.^[1]Two forms have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies. A variant form of DBQD, Kim variant, has been described in 7 patients originating from Korea and Japan, and is characterized by short stature, joint and minor facial anomalies, together with significant hand anomalies with short bones in the hands, long fingers and advanced bone age. DBQD type 1 and Kim variant are caused by mutations in the gene CANT1.  Some cases of DBQD type 2 are caused by mutations in the gene XYLT1 but in other cases the cause is unknown.^[2] It is inherited in an autosomal recessive manner.^[3] Type 1 can be associated with severe respiratory problems. Treatment for the condition is geared towards the signs and symptoms present in each individual.^[1]

The signs and symptoms of Desbuquois syndrome may vary in nature and severity and may include:^{[1][3][4][2][5]} 

• Intrauterine growth retardation;
• Short stature with shortened extremities (arms and legs). Adult stature is usually 114 cm or greater.;
• Generalized joint laxity, which can cause joint dislocations;
• Radial deviation of the fingers with thumbs that are often broad and in the "hitchhiker position";
• Narrow chest with pectus carinatum (which can lead to respiratory infections);
• Kyphoscoliosis;
• Distinctive facial characteristics including a round flat face, prominent eyes, micrognathia (small jaw), saddle nose, long upper lip, flat philtrum (area between the upper lip and nose), and short neck;
• Intellectual disability of various degrees;
• Obesity in adults.

Complications may include sleep apnea, frequent respiratory infections, strabismus, club foot, cleft palate, glaucoma, and cryptorchidism (undescended testicle).^[1]

There are two forms of Debuquois syndrome that have been distinguished on the basis of the presence (type 1) or the absence (type 2) of characteristic hand anomalies (accessory ossification center situated away (distal) from the second bone of the hand (metacarpal), bifid distal phalanx (the bone of the tip of the finger is divided in two parts), or thumb with delta-shaped phalanx). A variant form of the syndrome, Kim variant, has been described in 7 patients from Korea and Japan, and is characterized by short stature, articular and minor facial anomalies, together with hand anomalies, including short metacarpals (bones of the hand) and fingers with long bones (elongated phalanges) with advanced carpal bone age.^[2]

Desbuquois syndrome type 1 and Kim variant are caused by mutations in the CANT1 gene (located on chromosome 17q25.3). In some cases of Desbuquois syndrome type 2 there are mutations in the XYLT1 gene (located on chromosome16p12), but in other cases no cause has been identified, suggesting that there may be other unidentified genes that may also cause the condition.^[2]

Desbuquois syndrome is inherited in an autosomal recessive pattern.^[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected,
• 50% chance to be an unaffected carrier like each parent,
• 25% chance to be unaffected and not a carrier.

Only symptomatic treatment is currently available for individuals with Desbuquois syndrome. Many people with the condition may present with respiratory problems at birth or during infancy and need urgent attention. Severe scoliosis, a common complication, may be managed with physical therapy to control the progression of spine abnormalities. Arthrodesis (surgical fusion of a joint) may be considered for dislocations. Surgery may be considered for glaucoma. Because of the degree of shortness in affected individuals, psychological support may be appropriate for some individuals.^[1]