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Articles » Skeletal » Proximal femoral deficiency syndromes » Femoral - facial syndrome

2005-11-29-13 Femoral - facial syndrome © Cuillier

Femoral - facial syndrome

Cuillier F, MD*, Carasset G. MD**, Lemaire P, MD$, Deshayes M, MD$, Alessandri JL, MD#

* Department of Gynecology, Félix Guyon’ Hospital, Ile de la Réunion, France
** Gynecologist, Sainte-Clothilde clinic,IIe de la Réunion, France. 
$ Sonogapher, Moufia’ street, Ile de la Réunion, France.
# Department of Neonatology, Félix Guyon’Hospital, Ile de la Réunion, France.


Synonyms: Femoral hypoplasia - unusual facies syndrome

The increased risk for birth defects among infants of insulin-dependant diabetic mothers is well established. Infants of women who have insulin-dependant diabetes mellitus throughout pregnancy have a two or three times greater risk of congenital anomalies than infants in the general population. Among the congenital anomalies associated with maternal diabetes, heart disease and spine bifida are most common. Caudal regression and focal femoral hypoplasia are most distinctive but exceptional. 

We describe a case of prenatal diagnosis of bilateral proximal focal deficiency with left bowing femur in a diabetic woman. 

Case report

A 36-year-old woman, gravid 5, para 4 (four health children), was referred to our high-risk obstetric clinic at 26 weeks gestation to evaluate the fetal bones measurements. Before her fifth pregnancy, she negliged her diabetes mellitus. There was no history of prenatal teratogen exposure, drug ingestion, infection or other conditions that could be associated with malformation.

During the first trimester, the nuchal translucency measure and the triple test were normal. The second scan was only performed at 26 weeks gestation. The long bones were all short and then the patient was referred to our unit. We confirmed the anomaly. There were no bone fractures. The head was not macrocephalic. The profil showed micrognathia. The femurs were short bilaterally and the left one was curved. Measurement of all long bones were all bellow the 3rd percentile. There was no clubbed foot. No other associated structural abnormalities were observed. The placenta was hyperechoic.  All serologic screenings were negative (CMV, Herpes, MNI, Parvovirus).

During the pregnancy, patient’s blood pressure was normal and blood glucose was measured periodically (Levels glucose = 2g/l). The patient was treated with insulin in the end of the pregnancy. Subsequent ultrasound examination at 29 and 31 weeks showed lagging in all long bones, but fetal surveillance remained reactive. A spiral scan was performed but was not contributive. The sex is feminin. The last sonography was done at 37 weeks.

At 38 weeks, she delivered a female infant weighing 2400 g (Apgar scores at one and five minutes were 10 and 10 respectively). The infant showed bilateral short long bones (right and left femur). A Pediatric Orthopedic consultation confirmed the left bowing femur without fracture. Other long bones were symmetrical in their measurement.  Long–term follow-up was made with pediatric unit.

Ultrasound image of right and left femur showing abnormal right femur and shortening left femur and bowing.

3D Ultrasound image showing abnormal shortening right femur.

Profile view of the face. 3-D view showing the normal nose. Note the little microretrognathism on the sagittal facial view.

Aspect of the placenta at 29 and 31 weeks

2D view of the femur at 31 weeks. Note the left bowing femur accentuation.

3D view of the right and left femur at 31 weeks.

Spiral CT scan at 32 weeks showing no sign of other chondrodysplasia.

3D view of the genitalia at 37 weeks.

Post natal view of the legs of the baby. Infant’s lower extremities at birth showing shortening of both legs.

Radiography showing right femur and left bowing femur.


Although most fetuses of diabetic mothers exhibit growth acceleration, growth restriction occurs with significant frequency in pregnancies complicated by preexisting type 1 diabetes. The most important predictor of fetal growth restriction is underlying maternal vascular disease. Specially, pregnant patients with diabetes-associated retinal or renal vasculopathies and or chronic hypertension are most at risk for growth restriction.

Great diversity in the types of malformations is observed and none is considered to be a diabetes-specific anomaly. Among the congenital anomalies associated with maternal diabetes, heart diseases and spina bifida are most common. The most frequent types of skeletal anomalies are sacral hypoplasia, agenesis and hypoplastic limbs. Caudal regression and focal femoral hypoplasia are more distinctive but exceptional.  Although controversial, maternal diabetes mellitus has been implicated in fetal neurological (neural tube defect and holoprosencephaly), heart, kidneys and skeletal malformations.

First described by Daentl et al (1975), the "funny face syndrome" (FFS) was initially called FH-UFS4. When the full syndrome is observed, it comprises Pierre-Robin sequence, facial dysmorphism and femoral hypoplasia. In 1996, subsequently 19 observations have been published and most cases are female.
Burn et al divided the Femoral - facial syndrome in two groups, according to the presence or absence of facial dysmorphism. The true Femoral - facial syndrome is itself composed of three groups :

  • cases secondary of fetal constraint or deformation
  • cases resulting from maternal diabetes
  • disruption and those of unknown aetiology.

The hereditary nature of the syndrome has only been suggested in two instances The prenatal diagnosis of proximal femoral focal deficiency has been reported initially by Jeanty. These anomalies are thought to occur as a result of metabolic alteration (such as hyperglycemia, inhibition of arachidonic acid) of diabetes and its terotogenic effect on a susceptible developing embryo during the first trimester of pregnancy.

Landauer showed that injection of insulin into the yolk case could produce a syndrome of short upper beak with proximal limb defect, closely analogous to Femoral - facial syndrome. If the injection was performed earlier, absence of the sacrum, similar to that seen in the more classical caidal regression syndrome, was observed. Landauer postulated that the disturbance of glucose metabolism affected metabolic pathways common to proximal limb bud and facial development. The teratogenic mechanism is not clear, experimental studies have indicated that hyperglycemia itself is not a major component in producing diabetic embryopathies, which are induced instead by some other factors including genetic disposition and the components of the diabetic state, for example , ketone bodies, somatomedin inhibitors and low concentrations of insulin.

So we believe that our case is the consequence of maternal diabetes me