The Desbuquois syndrome is a rare autosomal recessive chondrodysplasia. It has a wide clinical spectrum characterized by short stature of prenatal onset with rhizomelic and mesomelic shortness, joint laxity, and characteristic facial dysmorphism including a round face, prominent, bulging eyes, and midface hypoplasia. Radiologically, Desbuquois syndrome is characterized by a "Swedish key" or "monkey wrench" appearance of the proximal femur and advanced carpal and tarsal bone age. Other characteristic hand changes include an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal phalanx of the thumb, and phalangeal dislocations, but these typical; features are only reported in a third of the patients. The pathogenesis of Desbuquois syndrome is unknown, but histological and transmission electron microscopy studies are suggestive of an impairment of the extracellular matrix.
Gillessen-Kaesbach et al. (1995) reported a male from a consanguineous family from Morocco with Desbuquois syndrome. The patient presented with micromelic short stature, flat midface, irregular ossification of the vertebral bodies and an advanced bone age. Faivre et al. (2003) further conducted a genome wide search on the patient of Gillessen-Kaesbach et al. (1995). An ancestral recombination event between loci D17S1806 and D17S1822 in the family defined the distal boundary of the genetic interval (9.5 cM). Nine genes were considered as possible candidates genes by their position and two more genes were considered as possible candidates by their function [See also: United Arab Emirates > Faivre et al. (2003)]. Faivre et al. (2003) concluded that the gene responsible for Desbuquois syndrome in the Moroccan family maps to chromosome 17q25.3.
Huber et al. (2009) carried out a mutation analysis of the Calcium-Activated Nucleotidase 1 (CANT1) gene in nine families with Desbuquois Dysplasia type 1. One of the patients was a Moroccan boy, birn to consanguineous parents, who died at the age of three months due to cardio-respiratory failure. The boy presented with joint dislocation in the elbow, hip and the right knee.
Faden et al. (2010) identified a newborn with classical features of Desbuquois dysplasia and born to parents who are first cousins. Sequencing of the CANT1 gene revealed a 5 bp duplication.
Faden et al. (2010) described a male Saudi neonate born to consanguineous parents with typical Desbuquois features. An ultrasound during the mother’s pregnancy revealed a micromelic fetus. Subsequently, the patient was born full term via spontaneous vertex delivery. The child showed severe growth retardation with abnormally short limbs and clubfeet. Facial dysmorphia included a rounded face, micrognathia, depressed nasal bridge, long philtrum and significant bluish corneal haziness in both eyes. An examination confirmed the presence of bilateral congenital glaucoma. X-rays of the hands revealed Desbuquois features, namely short metacarpals, two extra ossification centers distal to the second and third metacarpals, and delta phalanx formation in the first proximal phalanx. Multiple phalangeal dislocations were also found. The patient also had coronal clefting of the vertebral bodies, broad proximal femur with spur like projection of the lesser trochanters (‘monkey-wrench’ sign), tall ilia and flat acebular roof. Other features of note were a short neck, small chest, a protuberant abdomen and hypotonia. The patient succumbed to severe respiratory distress at 1-month of age. By carrying out homozygosity scanning and mutation analysis, a novel 5 bp duplication (c.893-894insGCCGC) was discovered in the CANT1 gene. This was predicted to result in a frameshift and premature truncation of the protein at codon 325. Both parents were found to be carriers of the mutation.
Al Kaissi et al. (2005) reported three Tunisian siblings with a rare assortment of clinical and radiographic abnormalities closely resembling Desbuquois dysplasia. The patients were the result of a second-degree consanguineous marriage. Two other siblings died of unknown causes soon after birth. The first patient was of an 8-year-old girl who had joint laxity and walking difficulties. At the age of 8 years she had a normal face, a very short neck, and narrow thorax. The second case was the brother of patient 1. At 7 years he had a short stature, multiple joint dislocations, kyphoscoliosis, and a normal face similar to that of his older sister. The third case was the sister of patients 1 and 2. She had hypotonia and joint laxity muscular dystrophy. All siblings had normal hands and were mentally normal. Radiographic examinations showed a generalized osteopenia with narrowing of the joint spaces and intervertebral discs. They also had prominent posterior cranial fossa and narrow cranial sutures. In addition, the patients had an additional remarkable radiographic feature not reported in Desbequois dysplasia-multiple carpal ossification centers. A 27-year-old brother refused to be investigated. He had a similar face to the affected siblings but no kyphoscoliosis or joint dislocations. Al Kaissi et al. (2005) proposed that the condition of their patients represents a novel Desbuquois-like syndrome.
In 1996, Al-Gazeli [should be: Al-Gazali] et al. (1966) reported a consanguineous Arab Bedouin family with Desbuquois syndrome. Affected members of the family had typical Desbuquois syndrome features including a midface hypoplasia and joint laxity. This was probably the first report on Desbuquois syndrome in Arab Bedouins. Faivre et al. (2003) further conducted a genome wide search in an affected male of the family of Al-Gazeli et al. (1996). The proband turned out to be homozygous for the marker D17S784. Nine genes were considered as possible candidates genes by their position, namely the STAT induced inhibitor-3 gene (SSI-3), the phosphatidylglycerophosphate synthase gene (PGS1), the dynein axonemal heavy polypeptide 17 gene (DNAH17), the Pleckstrin homology Sec 7 and coiled/coil domains 1 gene (PSCD1), the human tissue inhibitor of metalloproteinases 2 gene (TIMP2), the C1q and tumour necrosis factor related protein 1 gene (C1QTNF1), the apyrase gene (SHAPY), the lectin, galactoside-binding, soluble, 3 binding protein gene (LGAL3BP), and the chromobox homologue 8 gene (CBX8). TIMP2 was regarded as a good candidate gene by its function as the clinical features in Desbuquois dysplasia were consistent with a disorder of the extracellular matrix. Similarly, C1QTNF1was also considered as a candidate gene because of the presence of a collagenic domain and its expression in bone and cartilage. Direct sequencing on genomic DNA in TIMP2 and C1QTNF1 failed to detect any deleterious mutations in the patient. Faivre et al. (2003) concluded that the gene responsible for Desbuquois syndrome maps to chromosome 17q25.3 with a possible genetic homogeneity of the clinical subtype with hand anomalies.
Huber et al. (2009) reported an Emirati boy, born to consanguineous parents, with Desbuquois Dysplasia type 1. At birth his high was 4SD, he presented with mental retardation, joint dislocation in the hip and knee, but with limitation of the elbow, the boy also had walking difficulties. He had knees orthopedic surgery. In 2009, he was 17 years old.