Last updated:
07/24/2024
Years published: 1993, 2003, 2020
NORD gratefully acknowledges Cyril Boulila, MD Candidate, McGill University School of Medicine and Dr. Malte Spielmann, Max Planck Institute for Molecular Genetics, Berlin, Germany, for assistance in the preparation of this report.
Summary
Femoral facial syndrome (FFS) is a rare disorder that occurs randomly (sporadically) in the population. There have been, however, two patients reported in which the disorder appeared to be inherited in an autosomal dominant pattern. The major symptoms of this disorder are underdeveloped thigh bones (femoral hypoplasia) and unusual facial features.
Introduction
FFS is included in the “limb hypoplasia-reduction defects group” according to the newer classification of genetic skeletal disorders.
Femoral facial syndrome is a rare disorder characterized by underdeveloped thigh bones (femurs) and unusual facial characteristics. Patients have a very broad range and variety of symptoms. One source lists 31 clinical signs, classified as very frequent, relatively frequent and less frequent.
Clinical signs characterized as very frequent are (80-99%):
– Cleft palate
– Femur absent/abnormal
– Unusually small and/or retracted jaw (micrognathia/retrognathia)
– Short limbs (micromelia, femur especially)
– Abnormal vertebral size or shape
Clinical signs characterized as relatively frequent are (20-30%):
– Upwardly slanting eyelids (upslanted fissures)
– Thin lips + Long vertical groove in the middle of the upper lip (philtrum)
– Low-set and poorly formed ears / Small or virtually absent ears (microtia/anotia)
– Fused bones of the spine (sacrum and coccyx)
– Short stature (dwarfism)
– Hip dysplasia
– Femoral neck anomaly (coxa vara)
– Abnormal fibula morphology
– Deformation of the foot that may be turned outward or inward (talipes-equinovarus)
– Extra toes (preaxial foot polydactyly)
– Maternal diabetes
Clinical signs characterized as less frequent are (5-29%):
– Cross sided eyes (strabismus)
– Sprengel anomaly
– Rib fusion
– Radius and ulna bone fusion (radioulnar synostosis)
– Scoliosis
– Underdeveloped kidneys (renal hypoplasia)
– Kidney function anomaly (polycystic kidney dysplasia)
– Enlarged penis
– Enlarged heart ventricles (ventriculomegaly)– Cerebral (brain) structural abnormalities that can be seen in imaging tests.
Facial differences appear to be very variable, ranging from an evident Pierre Robin sequence with malformed ears to more subtle features. The more constant feature seems to be a small jaw (micrognathia). Pierre Robin sequence is characterized by micrognathia (which causes backward displacement of the tongue and upper airway obstruction that can lead to breathing problems) and usually a cleft palate.
The exact cause of FFS is not known. Most cases occur randomly. A genetic factor may be a cause in some patients, but it is more likely that multiple factors are involved.
About a third of the cases are linked to maternal diabetes, suggesting that diabetes can cause this syndrome. Features like the facial characteristics, cardiovascular defects and structural abnormalities in the brain support the theory that maternal diabetes can be a cause of FFS.
Some patients have been reported with a genetic change on the end of the long arm (q) of the chromosome 2, specifically 2q37.2. Further genetic studies are needed to identify the specific genes involved and their exact contribution to FFS.
While most cases of FFS occur at random, there are reports of several affected people in the same family suggesting autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Femoral facial syndrome is a very rare disorder that seems to affect more males than females. As of 1993, about 55 patients had been reported and one-third of are associated with maternal diabetes.
Diagnosis is based on the signs and symptoms. Clinical features of FFS vary widely and can involve all major body systems. Femoral hypoplasia is the key feature of FFS, where the thigh bones (femurs) are underdeveloped. This can range from complete absence (agenesis) of the femur to mild underdevelopment (hypoplasia).
For a diagnosis of FFS, femoral hypoplasia must be present along with at least two of the following four facial features:
Treatment
Orthopedic medical care including surgery may help alleviate some of the more serious bone deformities associated with femoral facial syndrome.
Treatment requires the coordinated efforts of a team of specialists. Pediatricians, dental specialists, surgeons, speech pathologists and others may systematically and comprehensively plan the child’s treatment and rehabilitation. Cleft palate may be repaired by surgery or covered by an artificial device (prosthesis) that closes or blocks the opening in the roof of the mouth.
Genetic counseling is recommended for patients and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Campbell Jr, RM. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:712-13.
JOURNAL ARTICLES
Ghali A, Salazar L, Momtaz D, Prabhakar G, Richier P, Dutta A. The Clinical manifestations of femoral-facial syndrome in an orthopaedic patient. Case Rep Orthop. 2021 Jun 14;2021:6684757. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219463/
Darouich S, Amraoui J, Amraoui N. Femoral-facial syndrome: Report of 2 fetal cases. Radiol Case Rep. 2019 Aug 14;14(10):1276-1282. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704398/
Luisin M, Chevreau J, Klein C, et al. Prenatal diagnosis of femoral facial syndrome: Three case reports and literature review. Am J Med Genet A. 2017 Nov;173(11):2923-2946. https://www.ncbi.nlm.nih.gov/pubmed/28948695
Spielmann M, Marx S, Barbi G, et al. Femoral facial syndrome associated with a de novo complex chromosome 2q37 rearrangement. Am J Med Genet A. May, 2016; 170A(5):1202-1207. https://www.ncbi.nlm.nih.gov/pubmed/26822876
Bonafe L, Cormier-Daire V, Hall C, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A. 2015;167A(12):2869-2892. doi:10.1002/ajmg.a.37365
https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37365
INTERNET
Femoral-facial syndrome. Orphanet. Last update: July 2009. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1988. Accessed August 18, 2020.
Femoral-facial syndrome. OMIM. Updated 01/08/2019. https://omim.org/entry/134780 Accessed August 18, 2020.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/No patient organizations found related to this disease state.
The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report
Your donation will help more than 30 million Americans with a rare disease navigate their diagnosis, receive financial assistance, and access the care and support they deserve. Make your tax-deductible gift today!