Affected individuals have extremely short limbs, ribs, and vertebra. Several subtypes exist. In general, achondrogenesis is characterized by premature birth, fetal hydrops, a normal sized, but unusually soft cranial vault and short neck and trunk. The disorder is often life-threatening already in utero or becomes so shortly after birth.
Chondrogenesis Imperfecta or Hypochondrogenesis or Achondrogenesis Type II (Langer-Saldino Type). Lethal Neonatal Dwarfism.
Three subtypes of achondrogenesis have been described:
Achondrogenesis Type IA: Houston-Harris Type
Achondrogenesis Type IB: Parenti-Fraccaro Type
Achondrogenesis Type II: Langer-Saldino Type; Chondrogenesis Imperfecta; Hypochondrogenesis
Inheritance in achondrogenesis Types IA and IB is autosomal recessive, whereas for achondroplasia Type II it is an autosomal dominant de novo mutation. The location of the genetic defect varies depending on the type. In Type IA the genetic defect has been mapped to the thyroid hormone receptor interactor 11 (TRIP11) gene on chromosome 14q32, which affects the assembly of the Golgi apparatus in chondrocytes and results in abnormal glycosylation and cellular transport of key matrix proteins. In Type IB, the gene locus maps to chromosome 5q32 affecting the diastrophic dysplasia/sulfate transporter (DTDST) gene, while in Type II the defect has been mapped to the collagen Type II alpha 1 chain (COL2A1) gene on chromosome 12q13.
The differential diagnosis includes several other forms of lethal chondrodysplasias and since this is a large group of disorders, the exact differentiation is not always straightforward, particularly in fetuses with ultrasound alone. It is the combination of the typical clinical, radiologic, and histopathologic (cartilage), genetic and biochemical findings that will eventually lead to the correct diagnosis.
This is a perinatal lethal condition, ie, if born alive, these babies usually die shortly after birth from profound respiratory failure. The reason for intrauterine death has not been determined, yet. It is not always possible to distinguish the different types of achondrogenesis based on clinical and radiologic findings alone. Premature birth is common. The clinical findings show significantly overlapping among the three types of achondrogenesis.
Achondrogenesis Type IA (Houston-Harris Type): Patients typically present with polyhydramnios and fetal hydrops and hypoplastic lungs commonly resulting in stillbirth or death in the immediate neonatal period. Clinical findings include a normal sized head with unusually soft calvarial plates (deficient ossification), flat face with protruding eyes, low-set ears, anteverted nares in a short nose, and bulging tongue. The chest is narrow (reduced circumference) due to short and horizontally oriented ribs (that are often fractured) and the abdomen is prominent with usually normal inner organs. Neck and trunk are short with only rudimentary ossification of the vertebral bodies (however, the pedicles of the cervical and upper thoracic vertebrae can ...