Introduction

Achondrogenesis, a fairly rare yet serious genetic disease, can leave expectant or new parents lost and afraid with many questions on how to care for their affected baby. What is this terrible disease and how can parents and healthcare staff care for these infants in the most nurturing and comforting way? To Answer these questions and to know more about this condition, check out the article below.

Definition of achondrogenesis

What exactly is achondrogenesis? Achondrogenesis is a genetic disease caused by mutations in several genes. These genes include TRIP11, SLC26A2, and COL2A1 and each of them are associated with a different variant of this disease. This genetic disorder affects the growth of bones and cartilage wherein the cartilage (chondro) is not (a) being made (genesis). This leads to stunted growth and dwarfism or short stature, affecting the arms, legs, ribs and vertebrae This leads to the main cause of complications and death in these children by respiratory failure. Many foetuses will die during pregnancy and any living baby will be at a higher risk for death in the immediate postpartum period.

Brief overview of neonatal care needs in genetic disorders

Infants with genetic disorders typically have some special care needs and will be admitted to the neonatal intensive care unit (NICU). However, these needs depend on the specific type of disorder and may include difficulty with breathing or eating by mouth. Specifically for achondrogenesis, some form of breathing help (such as with a ventilator) will be required due to the severely underdeveloped lungs seen in this condition. Care will be given in the context of palliative (or comfort) care.¹

Understanding achondrogenesis

As mentioned above there are two variations of achondrogenesis. The assigned type will be determined by the affected gene and if the specific case was acquired or randomly occurred during foetal development.

Types of achondrogenesis

The two types of achondrogenesis are defined as type 1 and type 2. Type 1 is further broken down into type 1A and type 1B. Type 1 occurs when a foetus inherits the mutation causing achondrogenesis from both mom and dad. Type 2 occurs randomly with a new mutation happening during cell division and growth. Type 1 is so infrequent that researchers are not sure how often it actually occurs in the population whereas type 2 is seen in about one of every 40,000-60,000 births.

Genetic basis and inheritance patterns

There are three main gene mutations which contribute to achondrogenesis. TRIP11 is linked with type 1A (Houston-Harris type), SLC26A2 causes type 1B (Fraccaro type), and COL2A1 is attributed to causing type t2 (Langer-Saldino type). In the case of types 1A and 1B, the inheritance pattern is autosomal recessive. This means that each parent has a defective copy of the gene and, although they appear normal, they each passed a defective copy onto the foetus. In the case of type 2, the autosomal dominant pattern is noted as only one copy of the faulty gene is necessary to cause the condition. This also occurs with a new, spontaneous mutation in the foetus and did not come from either parent.

It is thought that a TRIP11 mutation causes a malfunction in the Golgi apparatus which helps to prepare and export proteins to the correct area in the body. Specifically, in type 1A, the chondrocytes, or cartilage-producing cells, cannot work properly and bones cannot be formed correctly.

SLC26A2 which is associated with type 1B is thought to cause the skeletal malformations in achondrogenesis because there is a mutation in the gene responsible for a critical protein. This protein is required to cause cartilage to develop into bone. Since this protein is faulty the cartilage cannot be properly converted into bone and causes severe skeletal defects.

Lastly, in type two, the gene COL2A1 is mutated and cannot make collagen type 2 which is important for cartilage development. When this gene is mutated, which is typically random when compared to the genes causing type 1A and 1B, the connective tissue and bones cannot develop properly and the skeletal structure is critically damaged.

Neonatal care needs

Almost all cases of achondrogenesis are detected on a prenatal ultrasound done in the late first or early second trimesters. This allows parents and their medical team to be prepared for the level of care that will be required to ease the infant’s pain and other physical difficulties until they ultimately die.

Immediate medical interventions after birth

Many infants will die in utero and be stillborn. For the small percentage that survive, they will likely live for only a few short days. While this disorder is known for its skeletal abnormalities, the underlying organs and body structures are impacted as well. Historically, these babies can be born vaginally unless there is another medical reason for a caesarean section.

After delivery, if death is thought to be highly likely in a short interval, the baby may be left with the parents. The infant will be provided comfort/ palliative care and the parents will be provided with support.

On the other hand, if the infant is not expected to die within the immediate time frame after birth, they will be taken to the NICU and provided with supportive care, if the parents choose to pursue this level of care. The infant will undoubtedly receive respiratory support since their lungs are underdeveloped due to the small diameter of their chest and ribs. If they are given supportive care, and not palliative care, they will also be provided with nutrition, likely in the form of intravenous fluids.² Orthopaedic interventions may also be ordered if the baby is expected to survive. Since the infant is likely to be in pain, pain management is critical to any level of care provided to the infant and family. There will be numerous healthcare teams involved in the care of the infant if they are expected to survive for longer than a few days.

Importance of genetic counselling and family support

Since there can be a genetic component to achondrogenesis, specifically type 1, genetic counselling will be required to educate the family about the possibility of having future children with this disorder. In the case of type 1, only one copy of a defective gene from each parent is needed to affect the infant. However, since each parent would need to pass on the one defective copy, there is a 25% chance that another child would have achondrogenesis. In the case of type 2, it is improbable that another child will be affected since the first child’s mutation was completely random. 

In terms of family support, after the stillbirth or newborn death of their affected child, they will need strong support from their healthcare team. Ideally, this support should begin as soon as the diagnosis is made. One potential method to provide support is to connect parents who have had a child with achondrogenesis to speak with the expectant parents about what they can expect or after the infant loss to empathise and provide the level of support which only an individual who has experienced the situation can provide. There are also other support groups for families which may be specific to the disorder or more general and meant to support those experiencing infant or childhood loss. The organisations will vary depending on the country in which the family is located but in the United Kingdom there are several groups available. These include Little People UK, Genetic Alliance UK, Child Bereavement UK, or The Good Grief Trust.

Challenges in neonatal care

The biggest challenges in neonatal care for the infant with achondrogenesis will be to keep the baby as comfortable as possible and to support the family as the infant is actively dying. While respiratory support is the most critical component of the baby’s care, nutritional, orthopaedic, and pain management interventions, such as medications, may play a role as well. Pain management is especially important as the main goal of care for the infant and the family is to make the infant as comfortable as possible until they eventually die.

Respiratory management challenges

As mentioned above, the infant will need respiratory support which will most likely be delivered through an endotracheal tube in the mouth which is connected to a ventilator. However, if a family chooses to provide comfort or palliative care directly after delivery, then likely the infant will be left with the parents to live out their final moments.

Orthopaedic complications and management

In some cases, orthopaedics may be consulted to put splints on the baby’s limbs. In most cases, this is not done since the infant is expected to die within the first few days after birth and this would increase pain.

Long-term care

Unfortunately, in the case of achondrogenesis, all affected infants will die within a short time after birth. There are not currently any clinical trials available for this disorder and care continues to be geared to optimise the comfort of the infant and support the physical and psychological needs of the family.

Conclusions

Achondrogenesis is a rare and fatal genetic disorder usually detected by prenatal ultrasound but sometimes not noted until after delivery if the mother did not have optimal prenatal care. Because this disease causes severe skeletal deformities the organs and especially the lungs cannot develop properly. Infants are usually stillborn or die within the hours or days after birth. Infants should be provided with the respiratory and pain management support they require to keep them as comfortable as possible until they die. Parents and other family members must receive superb psychosocial support and genetic counselling to help them move through their grief and plan for any potential future pregnancies.