Achondrogenesis

Achondrogenesis refers to a group of rare and extreme skeletal dysplasias.

Epidemiology

The estimated incidence is 1:40,000, with no recognised gender predilection.

Pathology

It is classified as an osteochondrodysplasia, meaning deficiency of both bone and cartilage development. The condition has several recognised subtypes:

• type 1

  • type 1A: Houston-Harris subtype

  • type 1B: Parenti-Fraccaro subtype

• type 2: Langer-Saldino achondrogenesis

Genetics

Mutations in the SLC26A2 and COL2A1 genes cause achondrogenesis types 1B and 2, respectively. The genetic cause of achondrogenesis type 1A is still unknown. The patterns of inheritance are autosomal recessive in types 1A and 1B and autosomal dominant with de-novo mutations in type II2.

Radiographic features

Antenatal ultrasound

Sonographic diagnosis may be possible after 13 weeks of gestation, where nuchal oedema may be evident as an early (though non-specific) sign.

The fetal bony structures are often unable to be identified. There may also be extreme micromelia ⁵. Calvarial ossification may be preserved with the type II subtype which can, in turn, give a floating head appearance.

Additional sonographic findings include:

• micrognathia

• macrocephaly

• frontal bossing

• flat face

• anteverted nares

• long philtrum

• narrow fetal thorax

• lung aplasia/hypoplasia

• rib fractures may be present in type 1A

Other ancillary sonographic features that may be present include:

• polyhydramnios

• development of hydrops fetalis

Treatment and prognosis

The prognosis is generally poor, with most infants being stillborn or dying soon after birth.

History and etymology

AchondrogenesisThe term "achondrogenesis" was first described by Prof. Marco Fracaro (1926-2008)used in 1952 although it was previouslyby Marco Fraccaro (1926-2008 ¹²), a Professor of cytogenetics, who noted that a similar case had been published by G C Parenti in 1936 ². The 1B subtype is therefore also known as Parenti Fraccaro-Fraccaro syndrome.

Differential diagnosis

General considerations for mild cases include hypochondrogenesis. If there is calvarial bone absence (type 1A/1B) on antenatal ultrasound, consider acrania.

See also

• achondroplasia: a common cause of dwarfism; not to be confused with achondrogenesis

• achondrogenesis

  • type I1: 

    • type Ia1A: Houston-Harris subtype

    • type Ib1B: Parenti-Fraccaro subtype

  • type II2: Langer-Saldino syndrome