* Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. Department of Pathology, University of Mississippi Medical Center. Ph: 601-984-5300; Fax 601-984-5301.

Synonyms: Limb reduction abnormality.

Definition: Absence of one or more limbs.

Prevalence: 0.04-0.15:10,000 births¹.

Embryology: Arrest of formation of the primordium in the very early stages of embryo development, or disruption of normal development due to teratogenic, mechanical, or vascular accident¹. Cases with genetic linkage have been reported.

Associated anomalies: Multiple organ system defects have been  associated with amelia including cardiovascular, gastrointestinal, urogenital, skeletal, neural tube, and respiratory^1,2.

Differential diagnosis: Limb reduction defects.

Prognosis: Dependent on the presence or absence of other associated anomalies.

Recurrence risk: Not increased.

Management: Based on gestational age at diagnosis. Pregnancy termination should be offered if the diagnosis is made prior to viability. Cesarean delivery should be performed only for obstetrical indications.

MESH Ectromelia BDE 3285 (Limb reduction defect, of which, amelia is a severe form.) ICD9 755.4 CDC 755.400

Introduction

Amelia is the complete absence of the skeletal parts of the upper or lower limbs with no bony structure distal to the defect. Total amelia affects all four limbs¹. This unfortunate malformation generally is a random event, but is occasionally seen in specific syndromes associated with other congenital anomalies^1,2. This case report describes an early second trimester diagnosis of near total amelia in conjunction with other anomalies. Also presented are the obstetrical management and findings at autopsy.

Case report

A 31-year-old black female G₈ P₅₀₂₆ (one set of twins) was referred to the Antenatal Diagnostic Unit of the University of Mississippi Medical Center, Jackson, Mississippi with a diagnosis of "fetus without legsâ€. Past obstetrical history included term vaginal deliveries of appropriately grown infants in 1982, 1984, 1986, and 1987; delivery of twin male gestation in 1990; and two elective abortions in 1992. Pregnancy dating by last menstrual period and second-trimester ultrasound was consistent with 19 and a half weeks" gestation. The genetic and family history were unremarkable. The patient smoked half a pack of cigarettes daily during the pregnancy but denied use of alcohol, drugs, exposure to chemicals or X-rays during gestation.

A targeted ultrasound was performed using a 3.5 MHz sector and 5 MHz linear array (ATL Ultramark 9) and was consistent with 19 weeks and two days. The fetus was in a transverse lie with normal cardiac activity. The amniotic fluid volume was normal.

No upper or lower extremities were visualized with a possible limb bud seen for the left lower extremity (figs. 1 and 2). The scapulae were also absent. The spine was abnormally curved and consistent with scoliosis, but no specific neural tube defect was visualized. No other structural abnormalities were identified and the amniotic fluid volume was normal.

Figure 1: Scans demonstrating absence of extremities...

Figure 2: ...and scoliosis of the spine.

The patient elected pregnancy termination which was accomplished by intra-amniotic injection of prostaglandin F2a. The fetus and placenta were delivered intact 12 hours after the injection. Karyotype of a chorionic villus sample derived from the products of conception yielded a normal, 46 XX, female karyotype. The autopsy revealed a female fetus with a body size consistent with 20-21 weeks" gestation. Skeletal anomalies included no arms and no right leg (fig. 3). The left leg was very short with a 12 mm long cartilaginous femur (proximal transverse meromelia). Other abnormalities included severe micrognathia with microstomia and lower jaw ankylosis, bilateral rib fusions, and kyphoscoliosis (without abnormalities or vertebral ossification centers) (fig. 3-4). There were no soft tissue or histologic abnormalities.

Figure 3: X-ray of the fetus.

Figure 4: Posterior, lateral and anterior view of the fetus.

Discussion

Diagnosis

This case illustrates the sonographic diagnosis of near total amelia in the second trimester. Gross absence of the fetal limbs and the possibility of a left lower extremity limb bud was demonstrated on ultrasound. In addition, the spine was viewed as being abnormally curved, and these findings were confirmed at delivery and autopsy. Micrognathia was not diagnosed prenatally because fetal positioning during the ultrasound examination did not allow adequate visualization of the fetal face.

Embryology

Limb buds first appear during the third week of gestation with the upper limb buds appearing a few days before the lower limb buds. Complete absence of one or more limbs occurs prior to the eighth week of gestation¹.

Pathogenesis

Failure of formation of the limb primordia during early embryogenesis may be secondary to vascular, mechanical, or teratogenic exposure^3,4 with complete absence of one or more limbs occurring prior to the eighth week of gestation¹. Although the teratogenic potential of Thalidomide^® has been well documented, the spontaneous occurrence of amelia and limb reduction defects in the general population is rare^2,5. Most cases have no specific etiology, but some are seen in association with genetically transmitted disorders such as Robert"s syndrome⁶ and in families⁷.

Associated anomalies

Numerous anomalies have been associated with amelia. The findings of kyphoscoliosis and rib fusions in this case are consistent with other cases of amelia described in the literature^8‑10.

Prognosis

The presence of other associated anomalies affects neonatal morbidity and mortality. Infant death is reported to occur in up to 61% of cases complicated by amelia¹.

Management

This is based on the gestational age at the time of diagnosis with pregnancy termination being an option prior to viability. Cesarean section is reserved for obstetrical indications. Intra-amniotic prostaglandin F_2a was utilized uneventfully for pregnancy termination in this case.

_References

_{1. Froster-Iskenius UG, Baird PA. Amelia: Incidence and associated defects in a large population. Teratology 41:23-31, 1990.}

_{2. Ohdo-S; Madokoro-H; Sonoda-T; et al. Association of tetra-amelia, ectodermal dysplasia, hypoplastic lacrimal ducts and sacs opening towards the exterior, peculiar face, and developmental retardation. J Med Genet. 24:609-12, 1987.}

_{3. Pauli-RM; Feldman-PF; Major limb malformations following intrauterine exposure to ethanol: two additional cases and literature review. Teratology. 33:273-80, 1986.}

_{4. MilaireJ; Histological changes induced in developing limb buds of C57BL mouse embryos submitted in utero to the combined influence of acetazolamide and cadmium sulphate. Teratology 32:433-51,1985.}

_{5. Mastroiacovo P, Kallen B, Knudsen LB, Lancaster PA, Castilla EE, Mutchinick O, Robert E. Absence of limbs and gross body wall defects: An epidemiological study of related rare malformation conditions. Teratology 46:455-64, 1992.}

_{6. Gershoni-Baruch R, Drugan A, Bronshtein M, Zimmer EZ. Roberts syndrome or "X-linked amelia� Am J Med Genet 37:569-72, 1990.}

_{7. Zimmer-EZ; Taub-E; Sova-Y; Divon-MY; Pery-M; Peretz-BA; Tetra-amelia with multiple malformations in six male fetuses of one kindred. Eur J Pediatr. 144:412-4, 1985.}

_{8. Herring-JA; Goldberg-MJ; Amelia and scoliosis. J Pediatr Orthop. 5:605-9 , 1985.}

_{9. Powers-TA; Haher-TR; Devlin-VJ; Spencer-D; Millar EA; Abnormalities of the spine in relation to congenital upper limb deficiencies. J Pediatr Orthop 3:471-4, 1983.}

_{10.Nel-G; Du-Toit-G ;Congenital upper limb anomalies and scoliosis. S Afr Med J 63:893-5, 1983.}