What is femoral facial syndrome?

Femoral facial syndrome (FFS) is a rare congenital disorder^. characterised by the abnormal development of the femur bone (thigh bone) and deformed facial structure.¹ The characteristic features of the face include a short nose with a flat, board tip, an upward slant in the eyes, board space in between the nose and the upper lip which can also be called as philtrum, a cleft palate, pronounced facial structures,  smaller lower jaw (micrognathia) and smaller upper lips.² Several other defects in the body may include, deformed or abnormalities in the spinal bones, polydactyly which means extra fingers or toes, ear abnormalities, genitourinary defects, underdeveloped organs and patent ductus arteriosus (defect in the major blood vessel supplying the heart). The intellect of the patient is usually normal. The severity can depend on the extent of the deformity ranging from minor to more severe or complicated conditions.

What are the causes of femoral facial syndrome?

The cause of this disease is not clearly understood or known. Genetics may play a role and some cases have been associated with chromosomal abnormalities. It is usually associated with the end of the long arm (q) of chromosome 2, specifically 2q37.2.³ Sometimes multiple factors could lead to FFS. Most of the cases have also been reported for pregnant mothers associated with diabetes, suggesting that this could lead to the children developing this syndrome.⁴

Genetic mutations or other genetic syndromes, like caudal regression syndrome, could lead to FFS. Prenatal factors, including maternal conditions or exposure to medications, have been associated to be potential risk factors. Sometimes, it is believed to be sporadic, with no apparent genetic or environmental involvement.

Further research and genetic studies are required to identify the specific gene or cause of FFS. Although almost all cases occur at random, reports have shown that some of the affected cases are of the same family. This could suggest it is an autosomal dominant inheritance disorder (genetic disorder passed down by a parent to a child).  A single copy of a disease-causing gene variant is dominantly passed down. This could be inherited directly from the parent or through de novo where the gene goes through significant changes resulting in a changed gene. The percentage of risk of passing down the defective gene is around 50%. The risk remains equally the same for both males and females.

How is femoral facial syndrome diagnosed?

FFS is usually diagnosed at birth. Early diagnosis and intervention are key to better outcomes, with many individuals leading relatively normal lives with appropriate treatment and support.

The patient is first clinically evaluated. They are assessed for their distinct clinical features and bone deformities. Physical examination is important to note the limb length discrepancy, that is noting down the femur shortness or abnormality. There could also be gait abnormalities and mobility issues from the bone defect. Facial deformities that are characteristic of FFS are examined and evaluated. The presence of any two anomalies could suggest the presence of FFS. The extent of these features could depend on the severity of the disease. Any other skeletal abnormality associated with this disease, like a malformed bone in the upper or lower limbs or missing bones, could be present. A full thorough physical examination is required to identify all the defects associated with this condition.

A detailed prenatal and family history is very important to understand and confirm the diagnosis. Maternal history for any exposure or health conditions or complications is essential to identify all the risk factors. Familial history for congenital or genetic conditions could identify the hereditary pattern associated with FFS.

Radiographic images are important and vital to assess the extent of the skeletal abnormality. Through X-rays, the anterior and the posterior view of the affected bone could be visualised. They could help reveal the length, shape, and structure and are used as the primary diagnostic tool.  Prenatal ultrasound can detect skeletal abnormalities, in utero, but the full extent of the deformity could only be confirmed after birth. Magnetic Resonance Imaging (MRI) can help provide detailed images of soft tissues and bones to help determine the degree of bone involvement and identify any associated anomalies or any other bone involvement. Computed Tomography (CT) scans are cross-sectional images of the body that provide detailed images of the internal bone structures and any abnormalities associated with it.

Genetic testing can help in cases that may be suspected due to a genetic cause. Chromosomal Microarray Analysis (CMA) is a test that detects chromosomal abnormalities, such as duplications or deletions that may be associated with FFS. Whole Exome Sequencing (WES) can help identify mutations in a particular gene that could be linked to the condition. This test is specifically useful when family history suggests similar anomalies or multiple congenital abnormalities are present.

How is FFS managed and treated?

The treatment of FFS depends on the severity of the symptoms and the specific bone deformities that are associated with the condition. The approach is multidisciplinary including pediatricians, orthopedic surgeons, plastic surgeons, and other specialties,

Orthopaedic management in mild cases includes regular monitoring, especially in younger patients. Shoe lifts and braces could be used to manage minor length discrepancies and help improve walking. For major defects, surgery may be rewired to correct limb shortening, limb lengthening surgeries, or procedures like epiphysiodesis which is growth plate surgery can be considered. Physical therapy can help maintain joint function and muscle strength. Procedures like osteotomies, which involve cutting the bone and realignment, may be considered to correct bone deformities and improve function.

Facial defects like cleft lip and palate can be improved by surgical interventions and are usually done in early childhood to correct the cleft defect and improve feeding, speech, and facial appearance. Speech therapy may be required following the surgery to improve any associated difficulties. Any cosmetic concerns could be addressed by plastic surgery to correct facial asymmetry and other abnormalities.

Kidney and urogenital abnormality should be monitored regularly with regular renal ultrasounds and monitoring of kidney function is recommended. Treatment may involve surgical correction if required. Cardiac problems could be evaluated with regular check-ups and echocardiograms to monitor heart function. Surgery may be required to correct any defects.

Supportive care and rehabilitation is also considered through physical and occupational therapy to improve mobility, strength, and daily functioning. Psychological counseling and support groups can help support patients and help them cope with the challenges of living with the congenital condition. Special education may be essential for children with learning disabilities and developmental delays.

Genetic evaluation can help confirm the diagnosis and determine the risk of recurrence in future pregnancies. Genetic counseling can provide support and educate the family regarding the genetic aspects of the condition, family planning, and prenatal testing options.

Long-term follow-up and regular monitoring with ongoing follow-up are important to monitor growth, development, and any other emerging complications. Treatment plans should be regularly reviewed and adjusted as required for the patient’s growth and development.

Conclusion

FFS is a complex congenital condition that requires intricate care and a personalized treatment plan. Though the exact cause is often unknown, advancements in medical and surgical treatments offer procedures and methods for improving the quality of life for the patients. Early diagnosis is essential to provide care and ongoing support could be vital in managing the challenges associated with FFS. Ongoing research could help better understand the condition will lead to a more effective treatment and support for the patients affected by this rare disease.