Rare Pulmonology News

Disease Profile

Frontometaphyseal dysplasia

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

Neonatal

ICD-10

Q78.5

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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Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

Frontometaphyseal dysplasia (FMD) is a genetic disorder characterized by abnormalities in skeletal development and problems in other organs of the body.[1][2] It is part of a group of diseases called otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, and Melnick-Needles syndrome. In general, these disorders involve hearing loss (due to malformations in the tiny bones in the ears (ossicles)), cleft roof of the mouth (palate), and defects of the bones in the fingers and/or toes (digits). Frontometaphyseal dysplasia is distinguished from the other diseases of the group by the presence of joint deformities (contractures) that restrict the movement of certain joints. Other symptoms may include prominent brow ridges; wide-set and downward-slanting eyes; a very small lower jaw and chin (micrognathia); small, missing or misaligned teeth; bowed limbs; an abnormal curvature of the spine (scoliosis); obstruction of ureters; heart defects; and breathing problems. Males generally have more severe features than females.[1][3] FMD is caused by mutations in the FLNA gene. Inheritance is X-linked.[2] There is also a form of FMD caused by mutations in the gene MAP3K7 with is known as frontometaphyseal dysplasia 2 and it is is inherited in an autosomal dominant manner.[4][1] Treatment depends on the problems present and may include hearing aid and surgery to correct the facial findings and the bone defects.[1]

Symptoms

In general, males tend to be more severely affected than females. Females may present with the characteristic craniofacial features and scoliosis. The main symptoms in males include:[13030[2][3]

  • Skeletal dysplasia (enlargement of the bones in the frontal part of the skull, skull base sclerosis, as well as in the medial part (diaphysis) of the long bones and the part between the diaphysis and the end parts of the bones, small tips of the bones of the fingers)
  • Progressive contractures of the hand and other bones of the body over the first 20 years resulting in limited movement of the hand, fingers, wrists, elbows, knees, and ankles
  • Scoliosis
  • Limb bowing
  • Deformed fingers
  • Facial dysmorphism (big frontal, wide-spaced eyes, down-slanting eye slits, broad nose bridge and tip, small or less teeth than normal and occasionally craniosynostosis (when the sutures of the skull closed too early))
  • Hearing loss.

Other features include congenital heart malformation, congenital subglottic stenosis (narrowing of the airways), a slender body, with underdeveloped muscles around the shoulders and in the inside of the hands. Males with frontometaphyseal dysplasia can present with obstruction of the ducts connecting the ureters with bladder and enlarged kidneys (hydronephrosis). Intelligence is normal. 

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
Broad thumb
Broad thumbs
Wide/broad thumb

[ more ]

0011304
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Long fingers
0100807
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Prominent supraorbital ridges
Prominent brow
0000336
Scoliosis
0002650
Skeletal dysplasia
0002652
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect

[ more ]

0001627
Camptodactyly of finger
Permanent flexion of the finger
0100490
Coarse facial features
Coarse facial appearance
0000280
Dislocated radial head
0003083
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures

[ more ]

0002987
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks

[ more ]

0000293
Fused cervical vertebrae
Fused neck
0002949
Hydronephrosis
0000126
Keloids
0010562
Limitation of knee mobility
Limited knee movement
0010501
Limitation of movement at ankles
0010505
Limited wrist movement
Limited movement of the wrist
0006248
Metacarpophalangeal joint contracture
0006070
Metaphyseal widening
Broad wide portion of long bone
0003016
Pes valgus
0008081
Sclerosis of skull base
Dense bone of skull base
0002694
Short diaphyses
Short shaft of long bone
0000941
Short distal phalanx of the thumb
Short outermost bone of the thumb
0009650
Short metacarpal
Shortened long bone of hand
0010049
Short metatarsal
Short long bone of foot
0010743
Subglottic stenosis
0001607
Ulnar deviation of the hand
0009487
Ureteral obstruction
0006000
Urethral stenosis
Narrowing of the urethra
0008661
Wrist flexion contracture
0001239
5%-29% of people have these symptoms
Amblyopia
Lazy eye
Wandering eye

[ more ]

0000646
Arnold-Chiari malformation
0002308
Astigmatism
Abnormal curving of the cornea or lens of the eye
0000483
Bifid uvula
0000193
Craniosynostosis
0001363
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hypotrophy of the small hand muscles
Degeneration of small hand muscles
0006006
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Mixed hearing impairment
Hearing loss, mixed
Mixed hearing loss

[ more ]

0000410
Oligodontia
Failure of development of more than six teeth
0000677
Pes cavus
High-arched foot
0001761
Progressive bowing of long bones
0006383
Shoulder muscle hypoplasia
Underdeveloped shoulder muscle
0008952
Single transverse palmar crease
0000954
Spina bifida occulta
0003298
Sprengel anomaly
High shoulder blade
0000912
Percent of people who have these symptoms is not available through HPO
Ankle flexion contracture
0006466
Antegonial notching of mandible
0003779
Anteriorly placed odontoid process
0004608
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

0001166
Broad phalanges of the hand
Wide hand bones
0009768
Coat hanger sign of ribs
0006665
Cor pulmonale
0001648
Coxa valga
0002673
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

Treatment depends on the symptoms present in the person, and may include:[1][2]

  • Hearing loss aids for deafness
  • Surgery to correct the facial deformities including the frontal deformity
  • Surgery to correct the joint contractures, the limb bowing, and the scoliosis.

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.

Where to Start

  • Genetics Home Reference (GHR) contains information on Frontometaphyseal dysplasia. This website is maintained by the National Library of Medicine.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • 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 Frontometaphyseal dysplasia. Click on the link to view a sample search on this topic.

References

  1. Frontometaphyseal dysplasia. Orphanet. 2015; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1826.
  2. Robertson SP. Otopalatodigital Spectrum Disorders. GeneReviews. May 2, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1393/.
  3. Frontometaphyseal dysplasia. Genetics Home Reference. 2007; https://ghr.nlm.nih.gov/condition/frontometaphyseal-dysplasia.
  4. Frontometaphyseal dysplasia 2. OMIM. 2016; https://omim.org/entry/617137.

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