Introduction

Femoral facial syndrome (FFS)  is a rare sporadic syndrome also known as femoral hypoplasia-unusual face syndrome. FFS is characterised by skeletal malformations and other abnormalities in physical appearance. FFS was first diagnosed in the early 1960s. 

The syndrome is associated with maternal diabetes (where the mother suffers from diabetes during pregnancy) and is characterised by micrognathia, cleft palate, and other minor dysmorphisms.^1,2

FFS is similar to Caudal regression syndrome (CRS) which is another syndrome that is strongly associated with maternal diabetes. FFS has been observed to cluster in some families, as such it has been suggested that certain genetic factors can increase the risk of developing FFS. However, there is currently no evidence for FFS being caused by specific gene mutations.¹ FFS does not impair intelligence and is not associated with chromosomal or obstetric defects. While FFS does not usually affect the likelihood of survival of a newborn, deaths within a few hours to months after birth have been reported as a result of FFS.³ There is little information on patients with this condition in adulthood.

The syndrome FFS can be differentiated into proximal, bilateral, and unilateral forms. Unilateral FFS is the most common form, seen in 80-90% of FFS cases.⁴ The bilateral form is typically associated with cleft palates and when this form is diagnosed all bony structures in the child are measured if any deformed bone is suspected. 

Proximal FFS (PFSS) is linked to the development of the acetabulum (socket of the Hip bone) and femur. FFS affects  as few as 0.11-0.2 children in every 10,000 births.⁴ PFFS can be differentiated into Types 1, 2, 3, 4, and 5. Type 1 and 2 are less severe and can be treated effectively. In Type 3  the acetabulum is moderately dysplastic (meaning abnormal cells are present in the tissue) and the femoral head is present.⁴ However, in maturity, there is no connection between the shaft of the femur and the femoral head.⁴ In Type 4, the acetabulum is severely underdeveloped, and the femoral head is not present. In type 5, the most severe form, both the acetabulum and femoral head are absent.⁴

Characteristics of femoral facial syndrome

Facial characteristics

The distinguishing facial characteristics consist of a short nose with a broadened tip, elongated philtrum (groove between the nose and lip), thin upper lip, and micrognathia (a condition in which the lower jaw is smaller than the upper jaw).² As well as upward slanting of palpebral fissures (the area between open eyelids).²

Other physical abnormalities

FFS is associated with other deformities including; cleft palate, clubfoot, and pelvic and spinal abnormalities.² Case studies have also shown underdeveloped femoral (leg bone) cartilage and underdeveloped isles of Langerhans, which are responsible for secreting insulin in response to increased blood sugar levels.¹

Organ function 

There have been reports of malformation of the genitourinary system and Central nervous system (CNS) in individuals affected by FFS.¹

The characteristic femoral defects in FFS can appear as the sole abnormality or as one of many anomalies. Many of these are present in several uncommon diseases, including Caudal regression sequence, Antley Bixler syndrome, and kyphomelic dysplasia.⁵

Causes of FFS

It is most widely believed that FFS is linked to parental history, most significantly maternal diabetes (about 49% of patients in a case study of 23 males and 31 females were the child of a mother who suffered from diabetes). Poor nutrition and/or diabetic control during pregnancy  may lead to the unborn fetus developing FFS.⁴

Other causes include drug overdose or exposure to high-intensity radiation during pregnancy and focal ischemia.⁴ Some research has suggested that physical trauma between the 4^th and 8^th week of gestation could be causative of FFS.⁴

Risks of FFS

The physical deformities associated with FFS can limit quality of life and particularly affect mobility. One of the biggest risks FFS patients face is airway obstruction. Airway obstruction  may lead to an inability to feed, failure to thrive, dehydration, exhaustion, increased energy expenditure and  increased intra-abdominal pressure. This increased pressure can result in a greater risk of aspiration and gastro-oesophageal reflux, electrolyte imbalance, cor pulmonale and death.³

Diagnosis

Ultrasound examination

FFS can be detected in utero through ultrasound images that help to see the foetus and can detect skeletal malformations, uplifted cleft, and characteristic low set of ears.⁵ Apart from 3D ultrasound testing, there is no other diagnosis for prenatal FFS.⁵

Femur measurements 

FFS can be diagnosed by observing a discrepancy between the measurements of the femora of the foetus in utero.⁴

Skeletal radiographs (X-rays)

X-rays often aid in detecting anomalies in the infant's bone and the radiographs help to see detailed information to confirm the diagnosis.⁴

MRI

Magnetic resonance imaging (MRI) has been proposed as a method of choice for early diagnosis of proximal FFS.⁴

Postmortem

The diagnosis can be made during autopsy but only if prenatal testing indicates the presence of FFS prior to death.

Treatment and Management

The clinical manifestation of FFS makes it difficult for a clinician to make an accurate diagnosis and provide effective treatment. Understanding this vast range of presentations is crucial for spotting FFS early on and adapting management strategies for each patient’s symptoms.⁷

Patients with Type 1 and Type 2 deficiency are treated via surgeries by correcting the deformities to manage the length of the bones.

Patients with Type 3 are treated via metaphyseal epiphyseal synostosis (the fusion of two leg bone tissues) has been shown to give promising results.⁴

In Types 4 and 5 surgery is not possible due to the absence of the femur and acetabulum therefore amputation is performed above or below the knee followed by length correction via prostheses.⁴

In the bilateral form of FFS, surgery is performed to equalize the leg length, stabilize the feet and improve patellofemoral stability (stable movements of the pelvis and leg).⁴

Long-term prognosis after orthopaedic corrections is very good and if an adult patient with FFS goes on to have a child, there is no need for any specific pregnancy management and they should be able to carry to term healthily.⁴

During pregnancy, women should undergo regular checkups that could identify any severe cases of FFS to aid in early intervention and the best treatment plan.

FAQs

Who is affected by Femoral facial syndrome?

Infants are affected with FFS from birth and most commonly those whose mother is a diabetic. Other causes of FFS are drug overdose and exposure to radiation during pregnancy.

How common is Femoral facial syndrome?

It is very rare affecting 0.1-0.2 children in every 10,000 that are born.

What are the main characteristics of Femoral facial syndrome?

The primary characteristic of FFS is skeletal abnormalities particularly affecting the leg bones and hip joint. FFS is also commonly associated with distinctive facial features such as a short nose and upward-slanted eyes and cleft palates are not uncommon.

How is Femoral facial syndrome diagnosed?

FFS is typically diagnosed during prenatal ultrasounds, identifying key characteristics such as abnormal femur measurements, cleft palate and other skeletal abnormalities. After birth, FFS can be diagnosed through X-rays and MRIs to look for bone deformities.

What to do if you suspect your child has Femoral facial syndrome?

Most often a child with FFS will be identified during prenatal scans, at birth or during early checkups. If you have any concerns over the development of your infant or child then bring them to their GP for a checkup, to ensure they are progressing healthily.

Summary

Femoral facial syndrome (FFS) is a rare syndrome found during the early stages of life.  The syndrome is differentiated into unilateral, bilateral, and proximal FFS. In some cases, the syndrome can be treated and managed with prostheses or surgery, but in more severe cases the condition can be severely life-limiting and can result in death. In this article, we have discussed PFSS  its subtypes, and its management. 

Ultrasound Images can reveal foetus details like skeletal malformations, clefts, and abnormal ear placement. Diagnosis relies on femur measurement discrepancies. Diagnosis is often via prenatal tests or can be performed post-humously. X-rays provide detailed bone anomaly diagnosis. MRI is suggested for early proximal FFS detection. 3D ultrasound only prenatal FFS diagnosis. One should always seek advice from a medical professional If it is suspected that the child has FFS to get a proper diagnosis and treatment.