Characteristic features of infants with fetal retinoid syndrome include abnormalities of the craniofacial region, CNS, and cardiovascular system. The specific symptoms and physical findings can vary from one infant to another. Affected infants may not have all of the symptoms listed below.
Craniofacial abnormalities Some affected infants may display small, low-set ears (microtia) with narrowing (stenosis) of the ear canals or are born missing ears. Abnormalities of the middle and inner ears may also be present including hearing loss. Additional craniofacial findings include widely spaced eyes (hypertelorism), incomplete closure of the roof of the mouth (cleft palate), an abnormal groove in the upper lip (cleft lip), and/or underdevelopment of the middle area of the face (midface hypoplasia). Some affected infants may experience paralysis (palsy) of certain facial nerves.
Cardiovascular abnormalities Potential cardiovascular abnormalities following retinoid exposure include structural (anatomical) malformations of the heart such as transposition of the great vessels; hypoplastic left heart syndrome; ventricular septal defects (VSDs); and tetralogy of Fallot.
Hypoplastic left heart syndrome is characterized by underdevelopment of the left ventricle, the aortic and/or mitral valves, and the ascending aorta.
VSDs are abnormal openings that may occur in any portion of the ventricular septum, the fibrous partition that divides the heart’s two lower pumping chambers (ventricles). The size and location of the defect will determine the severity of symptoms. Small VSDs may close without treatment or become less significant as affected infants mature and grow. If a moderately-sized defect is present, the heart may be unable to pump blood effectively, resulting in an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), and/or failure to grow and gain weight at the expected rate (failure to thrive). In some children, without appropriate treatment, large VSDs may cause life-threatening complications during infancy.
Tetralogy of Fallot is a rare form of cyanotic heart disease. Cyanosis is the abnormal bluish discoloration of the skin and mucous membranes (lips and tongue) that occurs due to low levels of circulating oxygen in the blood. Tetralogy of Fallot consists of a combination of four different heart defects: a ventricular septal defect; obstructed outflow of blood from the right ventricle to the lungs due to an abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis); a displaced aorta that causes blood to flow into the aorta from both the right and left ventricles; and abnormal enlargement of the right ventricle.
CNS abnormalities Some infants with fetal retinoid syndrome may develop CNS abnormalities, including hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid (CSF) in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms. Excess fluid can increase pressure on the brain and can cause the head to swell. Infants with fetal retinoid syndrome may have below average intelligence, experience learning disabilities, and exhibit delays in reaching developmental milestones such as sitting or crawling. In some children, the forebrain (prosencephalon) may fail to develop resulting in holoprosencephaly.
Affected infants may also develop a condition known as microcephaly, where the head circumference is smaller than would be expected for their age and gender due to developmental issues. This can result in developmental and intellectual disabilities. Additional complications that may arise due to microcephaly including balance and coordination problems as well as seizures.
Additional abnormalities Infants with fetal retinoid syndrome may experience abnormalities of thymus function. The thymus gland is located below the thyroid gland in the neck in front of the chest and is the primary gland of the lymphatic system. The thymus gland makes white blood cells needed to protect the body from infection.
Additional abnormalities that may occur in some children include webbing of the fingers (syndactyly), skeletal malformations affecting the legs and spine, and/or low muscle tone (hypotonia). Some infants may also develop eye problems such as microphthalmia, a condition where one or both eyeballs are very small, leading to possible vision loss. Some infants are born with their eyes missing (anopthalmia).