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2001-03-15-11 Femoral hypoplasia - unusual facies syndrome © Sleurs

Femoral hypoplasia - unusual facies syndrome

Submitted by Elke Sleurs, MD, Luc De Catte, MD

*Vrije Universiteit Brussel  and &Women’s Health Alliance, Nashville TN

Synonyms: Femoral hypoplasia - unusual facies syndrome.

Definition: Femoral –facial syndrome is a rare syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism with a short broad-tipped nose, long philtrum, a thin upper lip and micrognathia[1].

Prevalence: sporadic[2], less than 70 cases have been reported in the literature [3] [4] [5] [6].

Etiology: unknown[7]. But an association with maternal diabetes has been reported several


Pathogenesis: multifactorial[10]; a suggestion is that a disruption of normal carbohydrate homeostasis at a critical point of embryogenesis may be important in the development of femoral hypoplasia-unusual facies syndrome as well as in the development of caudal regression syndrome2.

Sonographic findings: Most important findings are short and bowed femurs (unilateral or bilateral), dysplasia of he sacrum; short broad-tipped nose, long philtrum, a thin upper lip, micrognathia and cleft palate. Associated anomalies are numerous as described later.

Case report: A 38-year old primigravida was referred to the ultrasound department at 22 weeks of gestational age because of “abnormal lower limbs”. Her past medical history was unremarkable. She underwent twice a diagnostic laparascopy.

The pregnancy was conceived after in vitro fertilization. Karyotyping for advanced maternal age was performed by amniocentesis and demonstrated a normal male karyotype (46 XY with G-banding). Sonogram revealed bilateral short femurs (17mm) and endorotation of both feet. There was a discrete facial dysmorphism with micrognathia and flat forehead. Fetal growth was normal. Differential diagnosis was proximal femoral deficiency syndrome or femoral hypoplasia –unusual facies syndrome. Pregnancy was terminated by extra-amniotic prostaglandines. The patient delivered a male fetus weighing 450 grams with a total length of 245 mm, head circumference of 180 mm and abdominal circumference of 145 mm. Both femurs measured 25 mm. There were bilateral clubfeet and a bifid big toe. Facial malformations were micrognathia, a long philtrum, a thin upper lip, cleft of the soft palate and short nose. There were no other malformations. Pathological examination confirmed the diagnosis of femoral hypoplasia –unusual facies syndrome.

The first set of images demonstrates the right leg. The femur is not only too short but also bend. Note also the abnormal proximal hip joint.



The second set of images represents views of the left leg. Similar findings of the femur are present.


The face demonstrated micrognathia:



There is also a  2 MB.videoclip.

Differential diagnosis:

  • Proximal femoral deficiency syndrome:  shortening or absence of the femur due to abnormal development of the proximal portion, usually unilateral. It distinguishes from femoral hypoplasia - unusual facies syndrome in the absence of facial deformities[11]..
  • Caudal regression syndrome: characterized by structural anomalies of the caudal end and adherent structures due to disruption in the caudal portion of the neural tube early in pregnancy: agenesis or dysgenesis of the sacrum, abnormal vertebral bodies of the lumbar spine, pelvic deformities, femoral hypoplasia, club feet, flexion contractures of the lower extremities and decreased movements of the lower extremities. As femoral hypoplasia - unusual facies syndrome it has a strong association with diabetes. Renal, gastro-intestinal and genital anomalies can be associated.[12],[13]. The differentiation between femoral hypoplasia - unusual facies syndrome and caudal regression syndrome can be made if the facial and upper extremity abnormalities are detected.
  • Amniotic band syndrome: localized cranial, body wall or limb defects due to an amniotic disruption complex.
  • Femur-fibula-ulna syndrome (Fibula, congenital absence): asymmetric abnormalities of upper and lower limbs: hypoplasia or aplasia of the femur and fibula, absence of fingers until absence of arms, para-axial hemimelia of the ulna and fibula of the humerus.
  • Campomelic dysplasia: short-limbed dysplasia characterized by abnormal curvature of the long bones, mimicking fractures, particularly of the lower extremities such as femur and tibia. Other features are micrognathia, hypertelorism, cleft palate; short ribs, bell-shaped thorax; absence or hypoplasia of the fibula and scapulae, clubbed feet, (kypho)scoliosis Central nervous system, cardial and renal anomalies can be associated12,13
  • Osteogenesis Imperfecta: heterogeneous group of genetic disorders characterized by severe bone fragility, leading to abnormal ossification and multiple fractures. Most important ultrasound findings (in particular type 2) are trapezoid shaped skull with decreased ossification and increased visualization of the intracranial structures; broad, short, fractured long bones and angulation; decreased echoes of the long and trabecular bones; small bell-shaped thorax[14],[15],[16].
  • Splenogodal fusion limb defect syndrome: a bizarre syndrome characterized by fusion of spleen and gonad; ectromelia, tetramelic limbs deficiencies, terminal transverse hemimelia; micrognatia; deep, narrow, V-shaped palate and multiple unerupted teeth. An overlap between splenogodal fusion limb defect syndrome and both femur-fibula-ulna syndrome and femoral-facial syndrome has been suggested[17].

Associated anomalies: The list of associated anomalies is long:

·         A few reports demonstrated preaxial polydactyly as an associated anomaly4,5. 

·         Visceral abnormalities as polysplenia, superior placed adrenals, a single pelvic or inferiorly placed kidney(s), septated urinary bladder and anorectal agenesis are reported[18] as well as ventricular septal defect with valvar and infundibular pulmonic stenosis, pilonidal sinus, absence of the labia majora[19], small penis, testis and cryptorchidism7.

  • A more recent report demontrated the presence of partial agenesis of the corpus callosum, heterotopias of the brain, bilobed lungs, intestinal malrotation, and vertebral segmentation defects[20].
  • Other well known facial and skeletal associated abnormalities are cleft palate; bilateral syndactyly of the second and third toe, bifid great toe, clubfeet, short or absent fibula, shortening of humeri with restricted motion of elbows, constricted iliac base with vertical ischial axis, hypoplastic acetabulae, large obturator foramina and posterior tapering of ribs7 11

Recurrence risk: The majority of cases have been sporadic but autosomal dominance has been implied.1 [21] 

Prognosis and management: The patients have a normal intelligence7. Further management will depend on the presence and different types of associated malformations. Before viability the option of pregnancy termination can be offered to the parents. 

Reviewers: Luis Guillermo Diaz Guerrero, MD and Anupama Patil, MD.                                                                 

[1] Lampert RP. Dominant inheritance of femoral hypoplasia-unusual facies syndrome. Clin Genet 1980;17(4):255-8

[2] Hinson RM, Miller RC, Macri CJ. Femoral hypoplasia and maternal diabetes: consider femoral hypoplasia/unusual Facies syndrome. Am J Perinatol 1996;13(7):433-6.

[3] Trabelsi M, Monastiri K, Hammami A, Touzi C, Ben Hariz M, Gharbi HA, Bennaceur B. Femoral hypoplasia-unusual facies syndrome Ann Pediatr (Paris) 1989;36(10):693-6

[4] Sabry MA, Obenbergerova D, Al-Sawan R, Saleh QA, Farah S, Al-Awadi SA, Farag TI. Femoral hypoplasia-unusual facies syndrome with bifid hallux, absent tibia, and macrophallus: a report of a Bedouin baby. J Med Genet 1996 Feb;33(2):165-7

[5] Baraitser M, Reardon W, Oley C, Fixsen J. Femoral hypoplasia unusual facies syndrome with preaxial polydactyly. Clin Dysmorphol 1994;3(1):40-5

[6] Urban JE, Ramus RM, Stannard MW, Rogers BB. Autopsy, radiographic, and prenatal ultrasonographic examination of a stillborn fetus with femoral facial syndrome. Am J Med Genet 1997 Jul 11;71(1):76-9

[7] Jones KL: Smith’s recognazible patterns of human malformation. 5th edition, WB Saunders 1997, pp 310-11

[8] Johnson JP, Carey JC, Gooch WM 3d, Petersen J, Beattie JF. Femoral hypoplasia-unusual facies syndrome in infants of diabetic mothers. J Pediatr 1983 Jun;102(6):866-72

[9] Burn J, Winter RM, Baraitser M, Hall CM, Fixsen J. The femoral hypoplasia-unusual facies syndrome. J Med Genet 1984 Oct;21(5):331-40

[10] Tadmor OP, Hammerman C, Rabinowitz R, Fisher D, Itzchaki M, Aboulafia Y, Diamant YZ. Femoral hypoplasia-unusual facies syndrome: prenatal ultrasonographic observations. Fetal Diagn Ther 1993 Jul-Aug;8(4):279-84

[12] Benacerraf B. Ultrasound of fetal syndromes. Churchill Livingstone 1998. pp250-254

[13] Callen. Ultrasound in Obstetrics and Gynecology. Saumders, 4th edirion. Pp 364-5

[14] Elejalde BR, de Elejalde MM. Prenatal diagnosis of perinatally lethal osteogenesis imperfecta. Am J Med Genet 1983;14:353-59

[15] Hale AV, Medford ED, Izquierdo LA, Curet L. Osteogenesis Imperfecta.

[16] Silva SR, Jeanty P. Osteogenesis imperfecta.

[17] OMIM database 183300

[18] DePalma L, Duray PH, Popeo VR. Femoral hypoplasia-unusual facies syndrome: autopsy findings in an unusual case. Pediatr Pathol 1986;5(1):1-8

[19] Goldberg RB, Fish B, Cohen MM Jr, Shprintzen RJ. Bilateral femoral dysgenesis syndrome: a case report. Cleft Palate J 1978;15(4):386-9
[20] Gillerot Y, Fourneau C, Willems T, Van Maldergem L J. Lethal femoral-facial syndrome: a case with unusual manifestations. Med Genet 1997;34(6):518-9

[21] OMIM database 134780

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