National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Frontometaphyseal dysplasia

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]
Last updated: 2/6/2017
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. 
Last updated: 2/6/2017

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth
[ more ] 		0006482
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Absent/hypoplastic paranasal sinuses 0005453
Bowing of the long bones
Bowed long bones
Bowing of long bones
[ more ] 		0006487
Camptodactyly of finger
Permanent flexion of the finger
0100490
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Craniofacial hyperostosis
Excessive bone growth of the skull and face
0004493
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Prominent supraorbital ridges
Prominent brow
0000336
Reduced number of teeth
Decreased tooth count
0009804
Sensorineural hearing impairment 0000407
30%-79% of people have these symptoms
Abnormal form of the vertebral bodies 0003312
Accelerated skeletal maturation
Advanced bone age
Early bone maturation
[ more ] 		0005616
Elbow dislocation
Dislocations of the elbows
Elbow dislocations
[ more ] 		0003042
Fused cervical vertebrae
Fused neck
0002949
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hypoplasia of the musculature
Poorly developed skeletal musculature
Underdeveloped muscle
[ more ] 		0009004
Irregular metacarpals
Irregular long bones of hand
0006160
Long fingers 0100807
Long metacarpals
Elongated long bone of hand
0010493
Posterior vertebral hypoplasia 0008451
Scoliosis 0002650
Short distal phalanx of hallux
Small outermost bone of big toe
0010103
Short distal phalanx of the thumb
Short outermost bone of the thumb
0009650
Synostosis of carpal bones
Fusion of wrist bones
0005048
Ulnar deviation of finger
Finger bends toward pinky
0009465
5%-29% of people have these symptoms
Atrioventricular canal defect 0006695
Craniosynostosis 0001363
Hydronephrosis 0000126
Subglottic stenosis 0001607
Tracheal stenosis
Narrowing of windpipe
0002777
Ureteral stenosis
Narrowing of the ureter
0000071
Urethral stenosis
Narrowing of the urethra
0008661
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
Coarse facial features
Coarse facial appearance
0000280
Coat hanger sign of ribs 0006665
Cor pulmonale 0001648
Coxa valga 0002673
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption
[ more ] 		0000684
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches
[ more ] 		0000689
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures
[ more ] 		0002987
Genu valgum
Knock knees
0002857
Hirsutism
Excessive hairiness
0001007
Hydroureter 0000072
Increased density of long bone diaphyses
Increased density of shaft of long bone
0006440
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Knee flexion contracture 0006380
Large foramen magnum
Big foramen magnum
0002700
Long foot
Disproportionately large feet
large feet
long feet
[ more ] 		0001833
Long phalanx of finger
Long finger bone
0006155
Mitral valve prolapse 0001634
Partial fusion of carpals 0006207
Partial fusion of tarsals 0008097
Persistence of primary teeth
Delayed loss of baby teeth
Failure to lose baby teeth
Retained baby teeth
[ more ] 		0006335
Pointed chin
Pointy chin
Small pointed chin
Witch's chin
[ more ] 		0000307
Scapular winging
Winged shoulder blade
0003691
Selective tooth agenesis 0001592
Short chin
Decreased height of chin
Short lower third of face
[ more ] 		0000331
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Stridor 0010307
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
Wrist flexion contracture 0001239
X-linked recessive inheritance 0001419
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Last updated: 7/1/2020
FMD may be inherited in a X-linked manner when it is caused by mutations in the FLNA gene. This means that if a parent of a patient with frontometaphyseal dysplasia (FMD) has the FLNA mutation, the chance of transmitting the mutation in each pregnancy is 50%. When the mother has an FLNA mutation, males who inherit the mutation will be affected; females who inherit the mutation may have some features. Males with FMD transmit the disease-causing mutation to all of their daughters and none of their sons.[1][3] FMD type 2, caused by mutations in the  gene MAP3K7, is inherited in an autosomal dominant manner.[4]
Last updated: 2/6/2017

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 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.


Last updated: 2/6/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Frontometaphyseal dysplasia. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Frontometaphyseal dysplasia:
    International Skeletal Dysplasia Registry (ISDR)
     

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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Frontometaphyseal dysplasia. Orphanet. 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1826.
  2. Robertson SP. Otopalatodigital Spectrum Disorders. GeneReviews. May 2, 2013; http://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.