Overview

Femoral Facial Syndrome (FFS) is a multiple congenital anomaly syndrome with bilateral femoral dysplasia. Cardiac anomalies associated with FFS include septal defects including Atrial Septal Defect (ASD) and Ventricular Septal Defect (VSD).¹ Femoral Facial Syndrome (FFS) is a rare disorder that occurs sporadically or randomly in a population.

However, there have been cases of patients who have inherited the disorder by an autosomal dominant pattern. The major symptoms of this disease are underdeveloped thigh bones (femoral hypoplasia) and unusual facial features. According to the newer classification of genetic skeletal disorders, FFS is included in the “limb hypoplasia”) and unusual facial features group.² 

Symptoms of FFS

For patients with FFS, there are a variety of symptoms that can be experienced. These include: the clinical signs that are very frequent are:

• Cleft palate
• Femur (could be absent or normal)
• Micrognathia/ retrognathia (unusually small or retracted jaw)
• Short limbs (especially femur)
• Abnormal vertebral size or shape

There are many other clinical signs which are considered relatively frequent including upslanted fissures (upward slanting eyelids), philtrum, microtia/anotia (low set or poorly formed ears/ small or virtually absent ears), sacrum and coccyx (fused bones in the spine), short stature or dwarfism, coxa vara (femoral limb anomaly) abnormal fibula morphology, talipes-equinovarus, preaxial foot polydactyly (extra toes) and maternal diabetes.

Furthermore, there are clinical signs that are considered rarely frequent, including strabismus (cross-sided eyes), sprengel anomaly, rib fusion, and radioulnar synostosis (radius and ulna bone fusion) amongst others. 

Genetic and Environmental factors play a role in contributing to FFS. Genetic transmission could be sporadic which includes familial cases with dominant inheritance. The reason for dominant genetic disorders is when a single copy of a disease-causing gene variant is essential to cause the disease.¹ 

Even though most cases of FFS are random, there have been many cases that have shown autosomal dominant inheritance. However, along with a genetic factor, there is a possibility that more factors are involved. About a third of the cases have been linked to maternal diabetes which suggests that diabetes could be a cause of this syndrome. This is supported by the features of FFS which include facial characteristics, cardiovascular defects and structural abnormalities in the brain.²

Cardiac anomalies in congenital syndromes

Congenital heart disease is the most common congenital anomaly. The two most common heart defects which have been diagnosed in infancy include muscular and perimembranous ventricular septal defects and atrial septal defects. As with other congenital heart diseases, there are various environmental and genetic factors that contribute to the development of congenital heart disease. 

Some common environmental factors include maternal illnesses which could include diabetes, rubella, etc., or maternal intake of teratogenic agents including lithium, isotretinoin and antiseizure drugs. Maternal age is also known as a genetic factor in some genetic conditions however, it is unclear if it is an independent risk factor for congenital heart disease. There are certain numerical chromosomal abnormalities like trisomy 21 amongst others which are associated with congenital heart disease. 

The other factors seen in cases include subchromosomal deletions (microdeletions), subchromosomal duplications or single-gene mutations. However, there is no genetic aetiology that has been identified for around 72% of patients with congenital heart disease.³ As mentioned, the most common Cardiac anomalies associated with FFS include septal defects including atrial septal defect (ASD) and Ventricular Septal Defect (VSD). 

Diagnostic approaches for cardiac anomalies in FFS

The diagnosis is based on signs and symptoms of a disease. The characteristics of FFS can vary and can involve all the major body systems. One of the key features is femoral hypoplasia which is when the femurs (thigh bones) are underdeveloped. The range of the severity of this is from mild underdevelopment of the femurs (hypoplasia) to complete absence of the femurs (agenesis). 

To diagnose FFS, femoral hypoplasia any other two characteristics of the following must be present:

• Philtrum (long space) between the nose
• Thin upper lip
• Underdevelopment of the mouth and jaw
• Upslanting palpebral fissures (upward slanting of eye openings)²

Clinical management and treatment

Clinical manifestations of FFS can vary and can range from being common to very rare. FFS can cause varying degrees of femoral malformation which could range from hypoplasia to aplasia or agenesis.⁴ Thus, the management of FFS is based on the treatment of symptoms itself and there is no established standard.⁵ Thus, there is no established treatment for FFS and there is a multidisciplinary approach that is taken for the various orthopedic and maxillofacial problems faced by patients.⁴ 

Orthopedic medical care which includes surgery can help to improve the serious bone deformities that are associated with FFS. The treatment however involves a multidisciplinary care approach as mentioned above which includes coordinated efforts of paediatricians, dental specialists, surgeons, speech pathologists and others to decide the patient plan of treatment and rehabilitation. Furthermore, genetic treatment is also recommended for families and patients with FFS.²

One case of FFS reported by Garcia et al. of a 41-week-old newborn was studied. A nonsurgical route was taken to allow for growth after which the patient was scheduled for surgical bone lengthening of the lower limb at 5 years of age. The purpose of surgical treatments is to allow for autonomous movement of the patients and the recommended surgical treatments include femoralisation of the tibia and use of bilateral hip orthosis. Thus, the management and the treatment vary by the symptoms of the patients.⁵

Prognosis and long-term outcomes

For patients with FFS, cardiac anomalies such as atrial septal defects and ventricular septal defects can affect the prognosis. Thus, early detection along with appropriate medical and surgical intervention can help to improve outcomes. If heart defects are left untreated then they could lead to complications which would affect the quality of life and the life expectancy of patients. 

The prenatal diagnosis of FFS is possible such as in the first trimester of pregnancy. Furthermore, it has been associated with insulin-dependent diabetes mellitus during pregnancy. In such cases, an ultrasound scan would prove to be beneficial given its prognosis.⁶ 

Ongoing monitoring management including regular heart function chek-ups and physical therapy can help improve the well-being and overall quality of life of patients. Thus, multidisciplinary care for patients with FFS is essential for patients with FFS and for long-term management of FFS. 

Challenges and considerations and future directions

FFS cases are rare in adults and hence, limited in clinical practice. However, establishing proper guidelines to manage the disease based on present research and taking into account the increased risk factors for adults with FFS would allow for better management for patients with FFS. Another challenge is that FFS is rare in clinical practice, however, there should be clinical guidelines that should be established for paediatric and adult patients in order to properly manage FFS over a period of time.⁷

Thus, overcoming these challenges and further establishing guidelines to manage FFS along with approaching multidisciplinary care for patients with FFS would help to alleviate symptoms and manage FFS over a period of time. 

Summary

Femoral Facial Syndrome (FFS) is a rare congenital disorder, characterised by distinct facial features, associated with cardiac anomalies such as Atrial Septal Defect (ASD), and Ventricular Septal Defect (VSD). FFS occurs through autosomal dominant inheritance or sporadically.

Major symptoms include cleft palate, short limbs, and unusual facial features. Environmental factors, such as maternal diabetes, may play a role in FFS. Diagnosis relies on specific physical signs, with management involving a multidisciplinary approach to orthopaedic and maxillofacial issues. Early detection and treatment of cardiac defects are essential for improved outcomes. Establishing guidelines for care remains a challenge in managing FFS.