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1994-01-20-12 Femoral hypoplasia - unusual facies syndrome © Crum

Femoral hypoplasia - unusual facies syndrome

  Alicia Crum, RDMS

 Address correspondence to: Alicia Crum, RDMS, Baptist Hospital, Division of Maternal-Fetal Medicine, 2010 Church, Suite 323, Nashville, TN 37203-0338 Ph: 615-329-7833 Fax: 615-340-4637.

Synonyms: Bilateral femoral dysgenesis—unusual facies syndrome1.

Definition: Disorder consisting of hypoplasia or absence of the femurs bilaterally and distinguishing facial characteristics of a short nose with a broad tip, elongated philtrum, thin upper lip and micrognathia.

Prevalence: Unknown but rare. Females are more commonly affected than males1,2.

Etiology: The etiology is unknown, but there has been speculation of a link to maternal diabetes mellitus4,5. Most cases have been sporadic4,5.

Pathogenesis: The exact pathogenesis is unknown, but because of the nature of the anomalies, the insult must occur early in embryogenesis.

Associated anomalies: The list of associated anomalies is long and includes cleft palate, short or absent fibulas, clubfeet, shortening of humeri, restricted motion of elbows, constricted ilial base, vertical ischial axis, hypoplastic acetabulae, large obturator foramina, lower spine abnormalities and posterior tapering of the ribs3 (Table 2). Aside from skeletal anomalies, these infants may have cardiac and genitourinary anomalies.

Differential diagnosis: Differential diagnosis could include proximal femoral deficiency syndrome, caudal regression syndrome, coxa vara and, to a lesser extent, thanatrophoric dysplasia, achondrogenesis, osteogenesis imperfecta, achondroplasia and camptomelic dysplasia.

Prognosis: Aside from complications due to physical limitations, most patients do well. Intelligence is usually normal to above normal1,3-6.

Recurrence risk: The recurrence risk is unknown4.

Management: When detected before viability, the option of termination of pregnancy can be offered to the parent. The postnatal management is directed at the orthopedic, facial, cardiac and genitourinary complications.

MESH Femur abnormalities BDE 2027 ICD9 75534 CDC 755.380 MIM 134780 POS 3232


The first case of femoral hypoplasia—unusual facies syndrome was reported by Franz and O"Rahilly in 1961, but it was not recognized as a distinct entity until 1975 when Daentl et al reported their cases5,10.

Case report

A 27-year-old G3P2002 patient was referred to our office because of an elevated glucose tolerance test and abnormal findings seen on an ultrasound exam done at another facility. Our ultrasound examination revealed a fetus with BPD and abdominal perimeter consistent with 20 weeks gestation. The amniotic fluid volume was subjectively increased. The intracranial anatomy appeared normal, but the fetus presented with micrognathia (fig. 1).

Figure 1: The fetal profile demonstrates micrognathia.

 The kidneys and bladder were normal, but no stomach was identified. An abnormal widening of the lower spine was demonstrated, and the sacrum was not visualized. The cardiac anatomy appeared normal, but the position of the heart was abnormal, lying in a horizontal plane. The most significant abnormalities involved the lower extremities. The left femur was not identified (fig. 2). There was severe hypoplasia of the right femur, which was reduced to a short stubby remnant (fig. 3). The only long bones of the lower legs appeared to be tibiae (fig. 2-3).

Figure 2: Two views of the left leg. Note the abnormal proximity of the foot and the spine, and the presence of only the tibia in the lower leg. The femur could not be identified.

Figure 3: The right leg. Again, note the absence of femur and fibula and the abnormal proximity of the tibial extremity with the spine.

 The fibulae were questionably absent. Talipes were present bilaterally.

The upper extremities were seen with difficulty, but they appeared somewhat shortened. They presented in persistent flexion with fusion of the humerus, ulna and radius at the elbows (fig. 4). A transabdominal chorion villous sampling was performed, and chromosome analysis revealed a normal female karyotype. The patient elected to terminate the pregnancy.

Gross examination revealed a female fetus with abnormally shortened lower extremities, bilateral clubfeet and micrognathia. The upper extremities were fused at the elbows in an acutely flexed position. Postmortem radiographs (fig. 5) showed almost complete absence of the femurs. The fibulae were also absent bilaterally. There was no evidence of spina bifida, but there appeared to be fusion of vertebra in the lower spine. No autopsy was performed.

Figure 4: Bony fusion (arrow) is visible at the level of the left elbow.

Figure 5: X-ray after delivery. The bony fusion at the level of both elbows is visible. The right femur is severely hypoplastic (arrow), and the fibula is absent from both lower legs.


The exact etiology of femoral hypoplasia—unusual facies syndrome is unknown3-6,9,10,12. There has been correlation of the disorder with maternal diabetes3-9,12, but it may not be the only cause since there have also been cases reported involving non-diabetic mothers. Other causes may include fetal constriction or compression due to severe oligohydramnios4,7,8.

Figure 6: The fetus after delivery. Note the shortening of the femurs bilaterally, and the clubbing of the feet.

Figure 7: The hand with slight overlapping of the digits.

Figure 8: A close-up view of the legs and feet.


As with etiology, the pathogenesis of this syndrome is unknown. Research done by Landauer in the 1940"s showed that anomalies similar to those of femoral hypoplasia - unusual facies syndrome could be induced in chickens by injection of insulin into the yolk sac7. The timing of this insult was also of importance since injections given earlier in the embryologic period produced anomalies more similar to caudal regression, while those done a little later produced the femoral hypoplasia—unusual facies syndrome type anomalies7. However, in humans, maternal insulin does not cross the placenta, and fetal insulin is not detectable until 10 weeks, which is after the critical period of embryologic long bone formation12 (Table 2). This raises the possibility of maternal hyperglycemia or glucose homeostasis being the teratogenic factor in femoral hypoplasia—unusual facies syndrome7,12.

Table1: Embryology of long bone development




limb buds appear


mesenchyme condenses to form primative cartilage cells


osteogenesis begins

Differential diagnosis

Femoral hypoplasia - unusual facies syndrome has many similar features to another femoral abnormality, proximal femoral focal deficiency syndrome. Proximal femoral focal deficiency is a congenital shortening of the femur due to abnormal development of the proximal portion. It is usually unilateral, with only 10-15% presenting with bilateral involvement14. Severity ranges from a mild shortening of the femur (Type A) to absence of the acetabulum, femoral head and majority of the shaft (Type D)14 (fig. 9).

Figure 9: The Aitken classification of proximal femoral focal deficiency. In type A, a small portion of the femur is deficient below the femoral head. In type B, the segment is absent or larger. In type C, the femoral head is absent and the acetabulum affected, while in type D, the femoral head and the acetabulum are absent.

 Distinguishing femoral hypoplasia - unusual facies syndrome from proximal femoral focal deficiency and caudal regression (all of which have been associated with maternal diabetes) may be difficult since they have overlapping features. Femoral hypoplasia—unusual facies syndrome is thought by some to be a form of caudal regression and not a separate entity6. The distinguishing features of femoral hypoplasia—unusual facies syndrome not seen in proximal femoral focal deficiency or caudal regression are the facial characteristics3,6.

Several other forms of skeletal dysplasia such as coxa vara, thanatrophoric dysplasia, achondrogenesis, osteogenesis imperfecta, achondroplasia and camptomelic dysplasia should also be considered, but present with distinguishing characteristics.

Associated anomalies

The associated anomalies are listed in Table 2.

Table 2: Associated anomalies

·  Cleft palate

·  Short or absent fibula

·  Clubfeet

·  Shortening of humeri

·  Restricted motion of elbows

·  Constricted ilial base

·  Vertical ischial axis

·  Hypoplastic acetabulae

·  Large obturator foramina

·  Lower spine abnormalities

·  Posterior tapering of ribs


Femoral hypoplasia - unusual facies syndrome affected infants have normal to above normal intelligence3-6. Most complications arise from small stature and limited function of the lower limbs3, but most patients are ambulatory5. Problems with feeding and speech development may also arise due to facial anomalies4,5. Other complications of recurrent urinary tract infection and incontinence have also been reported4. However, in cases without serious complications, the life span is usually normal4.

Recurrence risk

The recurrence risk is unknown4. Most reported cases have been sporadic1,4,5,8, but in 1980 Lampert reported a case of father/ daughter femoral hypoplasia —unusual facies syndrome10. However, there is controversy as to whether this is a true case of femoral hypoplasia—unusual facies syndrome8,13. No definite genetic link has been established at this time.


Before viability the option of pregnancy termination can be offered to the parents. The postnatal management is directed at the orthopedic, facial, cardiac and genitourinary complications.


The author gratefully recognizes the assistance of Philippe Jeanty, MD, PhD in the preparation of this manuscript.


1. Burck U, Riebel T, Held K R, et al: Bilateral femoral dysgenesis with micrognathia, cleft palate, anomalies of the spine and pelvis, and foot deformities. Helv Paediat Acta 36:473-482, 1981.

2. Pitt DB, Findlay II, Cole WG, et al: Case report: Femoral hypoplasia—unusual facies syndrome. Aust Paediatr J 18:63-66, 1982.

3. Daentl DL, Smith DW, Scott CI, et al: Femoral hypoplasia—unusual facies syndrome. J Pediatr 86:107-111, 1975.

4. Jones KL: Smith"s Recognizable patterns of human malformation. 4th Ed. WB Saunders, Philadelphia, 1988, pp 268-9.

5. Say B: Femoral hypoplasia—unusual facies syndrome. in Buyse ML (Ed): Birth defect encyclopedia, Blackwell Scientific Publication, Dover, MA p 681, 1990.

6. DePalma L, Huray PH, Popeo VR: Femoral hypoplasisa - unusual facies syndrome: Autopsy findings in an unusual case. Pediatr Pathol 5:1-8, 1986.

7. Burn J, Winter RM, Baraitser M, et al: The femoral hypoplasia - unusual facies syndrome. J Med Genet 21:331-340, 1984.

8. Lord J, Beighton P: The femoral hypoplasia - unusual facies syndrome: A genetic entity?. Clin Genet 20:267-275, 1981.

9. Hurst D, Johnson DF: Brief clinical report: Femoral hypoplasia - unusual facies syndrome. Am J Med Genet 5:255-258, 1980.

10. Lampert RP: Dominant inheritance of femoral hypoplasia - unusual facies syndrome. Clin Genet 17:255-258, 1980.

11. Gleiser S, Weaver DD, Escobar V, et al: Femoral hypoplasia - unusual facies syndrome, from another viewpoint. Eur J Pediatr 128: 1-5, 1978.

12. Riedel F, Froster-Iskenius U: Caudal dysplasia and femoral hypoplasia - unusual facies syndrome: different manifestations of the same disorder? Eur J Pediatr 144:80-82, 1985.

13. Johnson JP, Carey JC, Gooch WM III, et al: Femoral hypoplasia - unusual facies syndrome in infants of diabetic mothers. J Pediatr 102:866-872, 1983.

14. Jeanty P, Kleinman G.: Proximal femoral focal deficiency. J Ultrasound Med 8:639-642, 1989.

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