Fetal aminopterin syndrome

Fetal Aminopterin Syndrome (FAS) is a rare, teratogenic condition caused by the maternal intake of aminopterin or methotrexate, drugs that inhibit dihydrofolate reductase, during pregnancy. This inhibition leads to a deficiency in folic acid, which is crucial for DNA synthesis and cell division, affecting fetal development.

Etiology

Fetal Aminopterin Syndrome is directly linked to the exposure of the developing fetus to aminopterin or methotrexate. These substances are antifolate drugs, used in the treatment of certain types of cancer, autoimmune diseases, and as abortifacients. The exposure typically occurs when these medications are administered to pregnant women, unaware of their pregnancy or the teratogenic risks associated with these drugs.

Pathophysiology

The pathophysiology of Fetal Aminopterin Syndrome revolves around the inhibition of dihydrofolate reductase by aminopterin and methotrexate. This inhibition leads to a reduced availability of tetrahydrofolate, a derivative of folic acid necessary for the synthesis of purines and thymidylate. These components are essential for DNA synthesis and repair, and their deficiency during critical periods of fetal development results in a spectrum of congenital anomalies.

Clinical Features

The clinical manifestations of Fetal Aminopterin Syndrome can vary but often include a combination of physical and developmental anomalies. Common features include:

• Craniofacial abnormalities such as craniosynostosis, a condition where the skull bones fuse prematurely, leading to an abnormal head shape; microcephaly, a significantly smaller head size indicative of brain development issues; and a cleft palate or cleft lip.
• Skeletal abnormalities like scoliosis (curvature of the spine), limb deformities, and digital anomalies (abnormalities in the fingers and toes).
• Growth retardation, both prenatally and postnatally, leading to low birth weight and short stature.
• Neurodevelopmental delays or intellectual disabilities due to the impact on brain development.

Diagnosis

Diagnosis of Fetal Aminopterin Syndrome is primarily based on the clinical presentation and a history of maternal exposure to aminopterin or methotrexate during pregnancy. Prenatal imaging, such as ultrasound or MRI, can reveal some of the physical abnormalities associated with the syndrome. However, the definitive diagnosis is often made postnatally through a thorough physical examination and the correlation of clinical findings with maternal drug history.

Management

Management of Fetal Aminopterin Syndrome is supportive and symptomatic, focusing on the specific needs of the individual. This may include surgical interventions to correct physical anomalies such as cleft palate or limb deformities, specialized care for growth and developmental delays, and supportive therapies like physical, occupational, and speech therapy to maximize the child's functional abilities.

Prognosis

The prognosis for individuals with Fetal Aminopterin Syndrome varies depending on the severity of the anomalies and the success of management strategies. Early intervention and supportive care can improve the quality of life and functional outcomes for many affected individuals.

Prevention

Prevention of Fetal Aminopterin Syndrome is primarily through the avoidance of aminopterin and methotrexate during pregnancy. Women of childbearing age who are on these medications should be counseled on the teratogenic risks and advised on effective contraception to prevent pregnancy. If pregnancy is planned or occurs, alternative medications should be considered in consultation with healthcare providers.

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