Aase Syndrome - Causes, Symptoms, Complications, and Treatment

What Is Aase Syndrome?

Aase syndrome is a very rare, autosomal dominant genetic disease that involves congenital hypoplastic anemia and triphalangeal thumbs. Hypoplastic anemia is a condition in which the body stops producing enough new blood cells, so the bone marrow contains very few blood cells. The triphalangeal thumb is a congenital anomaly in which the thumb has three phalanges or tubular bones instead of two. People suffering from Aase syndrome may have one or more skeletal and joint morphological deformities.

The disorder is named after the American child specialists Jon Morton Aase and David Weyhe Smith, who described it in 1968.

What Is the Medical Condition of the Patients Suffering From This Syndrome?

Individuals affected with this condition usually exhibit the presence of bilateral triphalangeal thumbs since birth, along with hypoplastic anemia that develops during the first six months of life. Affected individuals also present with severe joint and skeletal deformities and malformations, with delayed cranial fontanelle spot closures and poor peripheral venous access.

Fontanelles are the soft spots present on a newly born head where the bony plates that comprise the skull have not fused together. Poor venous access means that the patient has non-visible and non-palpable veins. They may also present with a ventricular septal defect in the heart chamber that can lead to congenital heart failure.

What Are the Other Alternative Names?

• Aase-Smith Syndrome.

• Aase Congenital Anemia.

• Blackfan-Diamond Anemia Variant.

• Aase-Smith type.

What Is the Frequency of the Aase Syndrome?

The prevalence of the disease is equal to or less than <1 / 1 000 000. Aase syndrome is very rare, with not more than 20 cases reported in the medical literature.

What Are the Causes of Aase Syndrome?

It has been reported that many cases of Aase syndrome occur without a known etiological agent and are not carried down through families. They are not inherited.

However, approximately 46 % of cases have been shown to be genetically inherited. Aase syndrome is reported to be an autosomal-dominant disorder. It has been reported in history that there might be an alteration in one of nine genes that is important for synthesizing the ribosomal proteins correctly. This condition is similar to the Diamond-Blackfan anemia variant, wherein a missing piece on chromosome 19 is observed in some individuals. Therefore, these two conditions are identical.

What Is the Pathophysiology of the Disorder?

The genetic basis of the disorder is not yet known. There is decreased erythropoiesis. Congenital hypoplastic anemia is caused due to the underdevelopment of the patient’s bone marrow. The bone marrow is the place where blood cells are formed in the body.

Therefore, in patients suffering from Aase syndrome, the bone marrow is not developed properly, due to which the red blood cells cannot mature properly, leading to hypoplastic anemia.

What Are the Symptoms of Aase Syndrome?

The syndrome generally involves the following symptoms:

1. Bilateral triple jointed thumbs (triphalangeal thumbs). This means one or both the thumbs have three bones (phalanges) rather than the usual two in the affected individual.

2. Skinny fingers with reduced creases over the finger joints.

3. The inability to completely extend the joints since birth is known as congenital contractures.

4. Delayed and slowed growth.

5. Skin looks pale.

6. Delayed closure of the cranial fontanelles. Fontanelles are the soft spots present on an infant's head where the bony plates that form the skull have not yet fused together.

7. Narrow and sloping shoulders.

8. Hypoplastic radius (radius is one of the bones of the lower arm which remains underdeveloped in this disorder).

9. Absent or small knuckles.

10. Cleft palate.

11. Cleft lip.

12. Malformed ears.

13. Droopy eyelids (Ptosis).

14. Ventricular septal heart defect (a hole between the bottom two chambers of the heart).

15. Hypoplastic anemia (a condition in which the bone marrow contains very few blood cells).

16. Congenital hypoplastic anemia and triphalangeal thumbs are the most commonly recurring symptoms of this syndrome.

17. Triphalangeal thumbs may cause difficulty in holding, grasping, and manipulating objects with their hands in a person who is affected with Aase syndrome.

18. The movement of the hands and arms is restricted because of the hypoplastic radius bone in such individuals.

19. The appearance is also compromised in the affected individuals because of the hypoplastic radius.

20. The narrow and sloping shoulders occur because of the presence of underdeveloped bones in that region of the body.

21. Slow and retarded growth in kids with Aase syndrome may be partly attributed to their congenital anemia and partly to their autosomal dominant genetic variant factor.

What Are the Possible Complications of Aase Syndrome?

• Complications related to congenital anemia include weakness, tiredness, lethargy, and reduced oxygen-carrying capacity of the blood.

• The white blood cells also reduce in numbers, thereby altering the body's ability to fight infection.

• A cardiac defect, if present, may cause numerous heart complications in the affected individual.

• Some cases in the literature have also been associated with stillbirth or premature death.

What Are the Diagnostic Tests Done for the Aase syndrome?

The doctor will perform a physical exam of the affected individual. He may suggest the following tests that include:

• Biopsy- A bone marrow biopsy should be performed to look for underdeveloped bone marrow defects.

• Blood Tests- A complete blood count (CBC) will demonstrate anemia and a reduction in the number of white blood cell counts.

• Echocardiogram- An echocardiogram should be advised to look for any congenital heart anomalies. The most commonly found heart defect is the ventricular septal defect.

• X-Rays- They should be taken to identify skeletal deformities. The triphalangeal thumb is an important clinical diagnostic sign that can be used to identify the syndrome.

What Is the Differential Diagnosis of Aase Syndrome?

There is clinical evidence of the overlapping of certain physical features between Aase-Smith syndrome I and Gordon syndrome. Gordon syndrome is a very rare genetic disorder that involves impaired mobility of certain joints of the distal extremities, including the knees, elbows, wrists, and ankles. The suggested features found in both syndromes include the presence of distal arthrogryposis and cleft lip or palate.

What Is the Treatment of Aase Syndrome?

There is no specific treatment for the disorder. However, in the absence of a specific cure, supportive care and surgical correction should be considered the best possible management for the affected individual.

• Blood Transfusions- They should be considered as a part of the treatment plan and should be administered in the first six months of life to treat hypoplastic anemia. Blood transfusions from a matched donor are carried out to treat serious anemia that does not respond to prescribed medications.

• Drug Therapy- Anemia that is associated with Aase syndrome is often controlled by the use of a steroid medication. However, they should only be prescribed after the healthcare provider properly reviews the benefits and risks associated with the medication.

• Bone Marrow Transplantation- A bone marrow transplant should be done for cases where other treatment options fail.

• Surgery- Orthopedic surgery, along with physical and occupational therapy, should be carried out for the affected individuals to manage the problems related to skeletal abnormalities. Heart defects and cleft lip and palate both require surgery and an extensive follow-up program, but they are correctable.

• Genetic Counseling- It should be recommended for any individual who wishes to get pregnant or a couple planning a baby who has a family history of Aase syndrome.

Conclusion

Aase syndrome is a rare genetic autosomal dominant disorder that poses a serious challenge for its diagnosis. It may be confused with other syndromes, also. Due to the lack of any specific diagnostic tests for the syndrome, it is very crucial to physically assess the patient properly. Genetic counseling is also very important for the family members as well as the affected individual. There is no treatment available for the disorder, so it is very important to provide supportive care to the patient in the best possible way. Cosmetic surgeries should also be carried out to improve the appearance and performance of the affected individual. More research is needed to identify the cause of this rare syndrome.