Filippi syndrome

Title

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Other Names:

Syndactyly type I with microcephaly and mental retardation; Unusual facial appearance, microcephaly, growth and mental retardation and syndactyly; Type 1 syndactyly-microcephaly-intellectual disability syndrome

Categories:

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary 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]

Last updated: 11/18/2020

Symptoms 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.

Last updated: 11/18/2020

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
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 growth retardation	Growth delay as children	0008897
Proptosis	Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ]	0000520
Single transverse palmar crease		0000954
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505

Showing of 57 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 1/1/2021

Cause 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]

Last updated: 11/18/2020

Inheritance Inheritance

Filippi syndrome is inherited in an autosomal recessive pattern.^[3] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must have a pathogenic variant to have the condition.

People with autosomal recessive conditions inherit one variant from each of their parents. The parents, who each have one gene variant, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 11/18/2020

Diagnosis 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]

Last updated: 11/18/2020

Treatment 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

Last updated: 11/18/2020

Statistics Statistics

It can be difficult to estimate the exact number of people affected by a rare condition. Some people may go undiagnosed or may be diagnosed incorrectly. Others may not seek medical care. The following estimate is based on the best information available in the medical literature. These estimates may change based on new medical information.

There have been about 30 cases of Filippi syndrome reported in the medical literature. It is unclear exactly how many people have Filippi syndrome.^[2]

Last updated: 11/18/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

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.

Clinical Research Resources

The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.

Organizations 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

About Face International
51 Wolseley Street
Toronto, ON M5T 1A4
Canada
Toll-free: 1-800-665-3223
Telephone: +1-416-597-2229
Fax: +1-416-597-8494
E-mail: info@aboutface.ca
Website: https://www.aboutface.ca/
Ameriface
PO Box 751112
Las Vegas, NV 89136
Toll-free: 888-486-1209
Telephone: 702-769-9264
E-mail: info@ameriface.org
Website: http://www.ameriface.org
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: faces@faces-cranio.org
Website: http://www.faces-cranio.org/

Do you know of an organization? We want to hear from you.

Learn More 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.

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Have a question? Contact a GARD Information Specialist.

References References

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.
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/.
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.
Battaglia A, Filippi T, Pusceddu S, Williams CA. Filippi syndrome: further clinical characterization. Am J Med Genet A. 2008; 146A(14):1848-52. http://www.ncbi.nlm.nih.gov/pubmed/18553552. Accessed 9/14/2011.