Perinatal lethal hypophosphatasia

Perinatal lethal hypophosphatasia (PLH) is one of the sub-types of hypophosphatasia. It is one of the most severe types.

The estimated incidence is at ~1:100,000 live births.


This sub type is thought to be due to an ALPL gene mutation location in chromosome 1q36 or the tissue non-specific alkaline phosphatase (TNSALP) gene. It carries an autosomal recessive inheritance. Patients with the heterozygous form of the disease are often normal or may be mildly affected.

  • carriers may have low levels of serum alkaline phophatase (ALP)
  • fetal ALP isoenzymes are often low on chorionic villus sampling
  • urine phosphoethanolamine is elevated

Patients with this type tend to have short limb dwarfism (micromelia) with very soft calvaria

Other features include:

  • blue sclerae 
  • spurs (Bowdler spurs) in the mid-portion of the forearms and lower legs
  • marked variability in the amount of bone ossification
    • general underossification of the bones of the fetus
    • limb shortening
    • lack of ossification of groups of vertebral bodies: may sometimes give a pattern of three ossified and three unossified vertebral bodies
    • lack of ossification of the neural arches of the spine
    • lack of ossification of the hands
    • marked demineralisation of the fetal calvarium and absent segments of the spine
  • variability between patients as to which bones were most severely affected
  • unusually dense, round, flattened, butterfly shaped; and sagittally clefted vertebral bodies
  • variability in femoral shape including "chromosome" like, "campomelic" like, and shortening with or without metaphyseal cupping or irregularities 
  • osteochondral projections of the midshaft of the fibula and ulna
  • bifid diaphyses 1
Ancillary antenatal imaging features include

This sub type is lethal there is no cure. There is a 25% recurrence risk for future pregnancies.

On antenatal ultrasound, it is difficult differentiate type of hypophosphaasia with conditions such as:

  • achondrogenesis type Ia
    • it is the bodies of the spine that are not ossified as opposed to the neural arches in hypophosphatasia
    • the calvarium will be ossified in achondrogenesis as opposed to hypophatasia where it will be absent.
  • osteogenesis imperfecta type II
    • in contrast to the thickened bones of osteogenesis type II, the long bones in hypophosphatasia tend to be thin or may be absent.
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Article Information

rID: 13872
Tag: cases
Synonyms or Alternate Spellings:
  • Perinatal lethal hypophosphatasia (PLH)

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