Severe Limb Shortening

Janice L. B. Byrne, MD

DIFFERENTIAL DIAGNOSIS

Common

Thanatophoric Dysplasia
Osteogenesis Imperfecta
Diabetic Embryopathy

Less Common

Achondrogenesis
Limb Reduction Defect

Rare but Important

Hypophosphatasia
Homozygous Achondroplasia
Amelia, Micromelia

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Is the shortening limited to a single bone, single limb, or generalized?
Are the long bones mildly shortened (1-3 standard deviations below the mean) or severely shortened?
Is the ossification normal?
Is the calvarium normally shaped?
Are there fractures?
Is there angulation or curvature of the long bones?
Are there other structural anomalies?
Is there a cystic hygroma or hydrops?

Helpful Clues for Common Diagnoses

Thanatophoric Dysplasia
- Most common prenatally diagnosed lethal skeletal dysplasia
- Polyhydramnios, often severe and progressive
- Type I
  - Normally shaped calvarium
  - Micromelia
  - “Telephone receiver” femur
  - Normal ossification, without fractures
  - Platyspondyly
  - Small chest with short ribs
  - Trident hand
  - Other malformations rare
- Type II
  - Cloverleaf-shaped calvarium (Kleeblattschädel)
  - Femora slightly longer and straighter than type I
  - Other features similar to type I
Osteogenesis Imperfecta
- Multiple subtypes with most severe manifestations in perinatal lethal type II
- Micromelia
- Generalized decrease in ossification of all bones
- Multiple fractures in utero
- Ribs with “beaded” appearance due to fractures
- Bones with irregular angulation due to fractures
- Superb visualization of brain by ultrasound due to underossified calvarium
Diabetic Embryopathy
- Uncontrolled diabetes is most common human teratogen
- Femoral hypoplasia common manifestation of embryopathy
  - Shortening may be severe
- Usually bilateral but may be asymmetrical
- Preaxial polydactyly
- Other structural anomalies involving central nervous system, heart, skeletal common
- Caudal regression
  - More common in uncontrolled diabetes
  - Sacral agenesis with shortened legs in fixed, crossed leg “tailor’s posture”

Helpful Clues for Less Common Diagnoses

Achondrogenesis
- Severe micromelia
- Vertebral ossification absent
- Small chest with short flared ribs, severe pulmonary hypoplasia
- Disproportionately large head with normal or deficient ossification
- Hydrops and cystic hygroma common in early gestation
- Type IA most severely affected with unossified spine and skull, multiple rib fractures
- Type IB without rib fractures
- Type II with normal skull ossification but unossified spine
Limb Reduction Defect
- May affect any segment of any limb
- Usually single limb affected
- Varying degrees of limb shortening
- Longitudinal, intercalary and terminal transverse defects possible
  - Greatest shortening with transverse defects
- May be seen with varicella exposure
- Amniotic band related amputation may have similar appearance

Helpful Clues for Rare Diagnoses

Hypophosphatasia
- 3 main subtypes: Perinatal, infantile, adult onset
- Perinatal onset associated with most severe limb shortening
- Micromelia and hypomineralization, often severe, often lethal
- Long bones thin and bowed
- Calvarium may be severely underossified
Homozygous Achondroplasia
- Autosomal dominant
- Both parents must have achondroplasia
  - 1/4 offspring with homozygous achondroplasia (lethal)
  - 1/4 with average stature (unaffected)
  - 1/2 with achondroplasia (heterozygous)
- Limb shortening severe, onset in the mid-trimester
- Chest is very small with associated pulmonary hypoplasia
Amelia, Micromelia
- Amelia: Absence of 1 or more limbs
  - Tetra-amelia rare
  - Associated anomalies very common (cardiac, orofacial clefts, genitourinary)
  - High risk pulmonary hypoplasia, perinatal death
- Micromelia: Shortening of both proximal and distal segments of limb
  - Association with severe, generalized syndromes
  - High risk perinatal lethality
- Phocomelia: Shortening of limb with hand or foot arising near trunk

Other Essential Information

Most important approach in prenatal evaluation of short limbs is to determine lethal vs. non-lethal condition
Severity of limb shortening and chest size most informative
Severe limb shortening associated with evidence of a generalized chondrodystrophy usually lethal
Small chest correlated with risk of pulmonary hypoplasia
Severe polyhydramnios common in lethal conditions
Pattern of involvement is critical in formulating differential diagnosis
- Are limb anomalies symmetric or asymmetric?
- Are upper or lower limbs more severely affected?
- Are the hands and feet present or absent; normal or abnormal?
Careful evaluation for other non-skeletal anomalies
Search for evidence of amniotic bands

Image Gallery

Clinical photograph shows a stillborn infant with thanatophoric dysplasia (TD). Micromelia

and a “trident” hand

are seen. The chest is bell-shaped

Coronal ultrasound shows a characteristic “trident” hand

of a fetus with thanatophoric dysplasia.

(Left) Ultrasound shows the very short radius and ulna

in the forearm of a mid-trimester fetus with TD. (Right) Axial ultrasound shows the normally ossified calvarium of a mid-trimester fetus with TD. The parietal prominences