Mesomelia-synostoses syndrome

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Mesomelia-Synostoses syndrome (MSS) is a syndromal osteochondrodysplasia due to a contiguous gene deletion syndrome, characterized by progressive bowing of forearms and forelegs leading to mesomelia, progressive intracarpal or intratarsal bone fusion and fusion of metacarpal bones with proximal phalanges, ptosis, hypertelorism, abnormal soft palate, congenital heart defect, and ureteral anomalies.

To date 5 unrelated patients have been reported, including one family with multiple affected persons.

In contrast to other mesomelic syndromes, MSS mostly manifests in postnatal life and has a slow progressive clinical course at least until adulthood (when skeletal growth has ceased). Craniofacial features include downslanted palpebral fissures, eyelid ptosis, telecanthus, soft palate hypoplasia with absent uvula (atypical posterior cleft palate) and mild micrognathia. Nasal speech is common. Skeletal anomalies comprise mild shortness of stature, progressive restriction of joint mobility, mesomelic bowing and shortening in upper and lower forelimbs, brachydactyly , ulnar deviation of the hands with a longest 2nd digit and clinodactyly of the 5th digit, narrow short feet, disproportionate brachydactyly of toes on the fibular side, and dysfunctional ankle joints. MSS patients may present with complex congenital heart defects, congenital hydronephrosis, unusual skin coverage on the umbilical cord stump, myopia, short sublingual frenulum and progressive hearing loss. Cognitive development is normal. Radiological anomalies include brachymetacarpalia and brachymetatarsalia of 3rd to 5th digits, synostoses between these bones, synostoses between metacarpals and metatarsals II to V and corresponding carpal/tarsal bones, partial fusion of carpal and tarsal bones, mild bowing of distal part of femora, and mild vertebral anomalies.

MSS is due to a non-recurrent microdeletion in 8q13. All patients have a deletion of two contiguous genes: SULF1 and SLCO5A1. Reported deletion sizes vary from 582Kb to 738 Kb. MSS is likely to represent a contiguous gene deletion syndrome. There is no disorder linked to point mutations of these genes.

Diagnosis is suspected on the basis of clinical and radiological findings and is confirmed by cytogenetic analysis (array CGH, FISH).

Radiologically, Kantaputra type mesomelic dysplasia (due to duplications of the HOXD locus on chromosome 2q; see this term) show very similar acral anomalies. Other rare mesomelic dysplasias, i.e., Langer mesomelic dysplasia or Fryns type micromelic dwarfism (see these terms) are not associated with synostoses. Syndromes with synostoses i.e. Nievergelt syndrome, proximal symphalangism, Osebold-Remondini syndrome and multiple synostoses (see these terms) have different associated anomalies.

Prenatal diagnosis of 8q13 microdeletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Preimplantation genetic diagnosis is available for at high risk couples. Bone anomalies are progressive and may be undetected on routine ultrasound scan.

MSS is transmitted as an autosomal dominant trait. When a parent is affected with MMS, recurrence risk is 50%.

Early diagnosis of MMS allows for more personalized surveillance and treatment. The life progressive course of MMS requires regular follow-up by appropriate specialists including a pediatric orthopedic surgeon to address the progressive deformities and functional restrictions in upper and lower limbs, maxillofacial surgery for palatal anomalies. Hearing loss must be monitored.

Life expectancy is unknown, but clinical manifestations appear to remain stable in adulthood.

Visit the Orphanet disease page for more resources.

Last updated: 10/1/2012

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