Mesomelia-synostoses syndrome

Alternate names

Mesomelia synostoses; Dominant mesomelic shortness of stature with acral synostoses, umbilical anomalies, and soft palate agenesis; Verloes-David syndrome

Definition

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.

Epidemiology

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

Cause

• 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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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

Signs and symptoms

• 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.

Clinical description

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormality of the humerus
• Abnormality of the metacarpal bones(Abnormality of the long bone of hand)
• Abnormality of tibia morphology(Abnormality of the shankbone)
• Aplasia/Hypoplasia of the uvula
• Brachydactyly(Short fingers or toes)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• High, narrow palate(Narrow, high-arched roof of mouth)
• Joint stiffness(Stiff joint)
• Mesomelia(Disproportionately short middle portion of limb)
• Metatarsal synostosis(Fusion of the long bones of the feet)
• Micrognathia(Little lower jaw)
• Micromelia(Smaller or shorter than typical limbs)
• Ptosis(Drooping upper eyelid)
• Short foot(Short feet)
• Short stature(Decreased body height)
• Skeletal dysplasia
• Synostosis of carpal bones(Fusion of wrist bones)
• Telecanthus(Corners of eye widely separated)
• Ulnar deviation of finger(Finger bends toward pinky)

30%-79% of people have these symptoms

• Abnormality of femur morphology(Abnormality of the thighbone)

Diagnosis

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

Treatment

• 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.

Prognosis

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

NIH genetic and rare disease info

• NIH info on Mesomelia-synostoses syndrome

Mesomelia-synostoses syndrome is a rare disease.

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