Disease Profile

Filippi 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

Q87.8

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.

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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)

Type 1 syndactyly-microcephaly-intellectual disability syndrome

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

Filippi syndrome is present at birth and impacts the development of the head, face, and limbs. Signs and symptoms include a small head (microcephaly), webbing of the fingers and toes (syndactyly), intellectual disability, growth delay, and distinctive facial features (high and broad nasal bridge, thin nostrils, small chin or micrognathia, and a high frontal hairline). Other features may can include vision problems, extra fingers and toes, and seizures. Because Filippi syndrome is very rare, it is not known how this condition changes over time. Filippi syndrome is caused by a genetic variant in the CKAP2L gene and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Filippi syndrome. These features may be different from person to person. Some people may have more symptoms than others, and they can range from mild to severe. This list does not include every symptom that has been described in the condition.

Symptoms may include:[1][2]

  • Small head size
  • Webbing or fusion of the fingers and/or toes (syndactyly)
  • Distinctive facial features with a small chin (micrognathia)
  • Intellectual disability
  • Speech delay
  • Growth delay

Growth delays typically start before birth and older individuals with Filippi syndrome may be shorter than average. Other symptoms have been reported in Filippi syndrome including dental abnormalities, vision problems, extra fingers and toes, and seizures.[2] Because few people with this condition have been reported, it is not clear how this condition changes over time.

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
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Dysphasia
0002357
Echolalia
Echoing another person's speech
0010529
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Mutism
Inability to speak
Muteness

[ more ]

0002300
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Specific learning disability
0001328
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
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
Wide nose
Broad nose
Increased breadth of nose
Increased nasal breadth
Increased nasal width
Increased width of nose

[ more ]

0000445
30%-79% of people have these symptoms
Aplastic/hypoplastic toenail
Absent/small toenails
Absent/underdeveloped toenails

[ more ]

0010624
Bilateral single transverse palmar creases
0007598
Broad columella
0010761
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Clinodactyly of the 5th toe
0001864
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Enlarged epiphyses
Large end part of bone
0010580
Frontal bossing
0002007
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Limb dystonia
0002451
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Muscular hypotonia
Low or weak muscle tone
0001252
Optic atrophy
0000648
Paraplegia
Leg paralysis
0010550
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Short philtrum
0000322
Small nail
Small nails
0001792
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
5%-29% of people have these symptoms
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Finger syndactyly
0006101
Hypertrichosis
0000998
Hypodontia
Failure of development of between one and six teeth
0000668
Seizure
0001250
Sparse hair
0008070
Supernumerary nipple
Accessory nipple
0002558
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

0000233
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
2-4 toe syndactyly
Webbed 2nd-4th toes
0010714
Autosomal recessive inheritance
0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cutaneous syndactyly
0012725
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile

[ more ]

0004325
Dystonia
0001332
Finger clinodactyly
0040019
Frontal hirsutism
Hairy forehead
0011335
Low hanging columella
0009765
Microdontia
Decreased width of tooth
0000691
Postnatal g

Cause

Filippi syndrome occurs when the CKAP2L gene is not working correct. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[3] 

Diagnosis

Filippi syndrome is diagnosed based on the symptoms, clinical exam, imaging studies and may be confirmed by the results of genetic testing.[1][2]

Treatment

Treatment of Filippi syndrome is focused on managing the symptoms. Options may include surgery to correct fused fingers and physical and speech therapy.[1][2]

Specialists involved in the care of someone with Filippi syndrome may include:

  • Neurologist
  • Orthopedics
  • Dentist
  • Hand surgeon
  • Physical therapist
  • Occupational therapist
  • Speech therapist

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    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

    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      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 Filippi syndrome. Click on the link to view a sample search on this topic.

        References

        1. Capecchi G, Baldassarri M, Ferranti S, Guidoni E, Cioni M, Nürnberg P, Mencarelli MA, Renieri A, Grosso S. CKAP2L mutation confirms the diagnosis of Filippi syndrome. Clin Genet. May 2018; 93(5):1109-1110. https://pubmed.ncbi.nlm.nih.gov/29473684.
        2. Sabir A, WalkerJK, Hart R.. Expanding the phenotype of Filippi Syndrome: a patient with early onset puberty. Clin Dysmorphol. Oct 2019; 28(4):224-226. https://pubmed.ncbi.nlm.nih.gov/30921095/.
        3. Hussain MS, Battagla A, Szczepanski S, Kaygusuz E, Toliat MR, Sakakibara S, et al. Mutations in CKAP2L, the human homolog of the mouse Radmis gene, cause Filippi syndrome. Am J Hum Genet. Nov 6, 2014; 95(5):622-632. https://pubmed.ncbi.nlm.nih.gov/25439729.
        4. Battaglia A, Filippi T, Pusceddu S, Williams CA. Filippi syndrome: further clinical characterization. Am J Med Genet A. 2008; 146A(14):1848-52. https://www.ncbi.nlm.nih.gov/pubmed/18553552. Accessed 9/14/2011.