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Disease Profile

Mesomelia-synostoses syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q74.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

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

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

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

Orpha Number: 2496

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.

Clinical description
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.

Etiology
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.

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

Differential diagnosis
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.

Antenatal diagnosis
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.

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

Management and 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.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the humerus
0003063
Abnormality of the metacarpal bones
Abnormality of the long bone of hand
0001163
Abnormality of tibia morphology
Abnormality of the shankbone
Abnormality of the shinbone

[ more ]

0002992
Aplasia/Hypoplasia of the uvula
0010293
Brachydactyly
Short fingers or toes
0001156
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Mesomelia
Disproportionately short middle portion of limb
0003027
Metatarsal synostosis
Fusion of the long bones of the feet
0001440
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Micromelia
Smaller or shorter than typical limbs
0002983
Ptosis
Drooping upper eyelid
0000508
Short foot
Short feet
Small feet

[ more ]

0001773
Short stature
Decreased body height
Small stature

[ more ]

0004322
Skeletal dysplasia
0002652
Synostosis of carpal bones
Fusion of wrist bones
0005048
Telecanthus
Corners of eye widely separated
0000506
Ulnar deviation of finger
Finger bends toward pinky
0009465
30%-79% of people have these symptoms
Abnormality of femur morphology
Abnormality of the thighbone
0002823
5%-29% of people have these symptoms
Abnormal eyebrow morphology
Abnormality of the eyebrow
0000534
Abnormal oral frenulum morphology
0000190
Abnormality of cardiovascular system morphology
0030680
Abnormality of the ankles
0003028
Bulbous nose
0000414
Convex nasal ridge
Beaked nose
Beaklike protrusion
Hooked nose
Polly beak nasal deformity

[ more ]

0000444
Genu valgum
Knock knees
0002857
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hydronephrosis
0000126
Long philtrum
0000343
Malar flattening
Zygomatic flattening
0000272
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Narrow mouth
Small mouth
0000160
Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]

0000325
Umbilical hernia
0001537
1%-4% of people have these symptoms
Short umbilical cord
0001196
Percent of people who have these symptoms is not available through HPO
Abnormal abdomen morphology
Abnormality of abdomen structure
0001438
Abnormal vertebral morphology
0003468
Absent uvula
0010292
Autosomal dominant inheritance
0000006
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Mesomelic short stature
0008845
Metacarpal synostosis
Fused long bones of hand
0009701
Microretrognathia
Small retruded chin
0000308
Nasal speech
Nasal voice
0001611
Partial fusion of proximal row of carpal bones
0005694
Progressive forearm bowing
0005891
Ulnar deviation of the hand
0009487

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Mesomelia-synostoses syndrome. Click on the link to view a sample search on this topic.