Introduction
The human body has 46 chromosomes in each cell. Chromosome 22 is the second smallest human chromosome. Trisomy 22 is a chromosomal disorder where a third copy of chromosome 22 is present in every cell or some cells of the body instead of two copies. Symptoms begin at birth, and the mild cases go unreported. The infants affected with this condition have various developmental anomalies. The disease can cause spontaneous abortions.
What Is Trisomy 22?
Trisomy 22 is a rare chromosomal disease in which chromosome 22 appears thrice rather than twice in body cells. It is the most common cause of first-trimester miscarriages. The disease can be of complete or mosaic type. There is also a possibility for developing partial trisomy 22, where two complete copies of chromosome with one incomplete copy are present. Depending on the number of cells that get affected, the symptoms can be of minor type, or health conditions that develop may be incompatible with life. Live births are rarely reported due to the development of severe organ malformations. The condition predominantly affects females. The reported life expectancy ranges from a few minutes to three years.
What Is the Cause of Trisomy 22?
Trisomy 22 can occur due to an error during the division of reproductive cells or during cellular division after fertilization. During abnormal cell division, an extra chromosome develops in reproductive cells. When an egg or sperm with extra chromosomes fuse, they form a trisomy 22.
A 'trisomy rescue' process may try to eliminate extra chromosomes. However, this process remains incomplete, leaving some cells forming mosaic trisomy 22. The condition can also occur due to uniparental disomy (both chromosomes are inherited from a single parent).
What Are the Types of Trisomy 22?
Mosaic Trisomy 22: In mosaic trisomy 22, the three copies of chromosome 22 appear in only a few cells. The other cells have a normal pair of two chromosomes. The disorder most frequently occurs in females. The symptom of trisomy 22 depends on the number of cells affected.
The characteristic features of this form of trisomy are prenatal and postnatal growth failure or delay, asymmetrical development of two sides of the body, and congenital heart defects. Few children may present with abnormal cognitive development, whereas a few may have normal cognitive development. Most children presented with intrauterine growth restriction (baby does not grow as expected) and developmental delays. Asymmetrical body development is seen, and unilateral hearing impairment is common.
Congenital heart defects are commonly seen in patients with trisomy 22. Atrial and ventricular septal defects are the most common cardiac malformations.
Dysmorphic features of the skin fold of the upper eyelid covering the inner corner of the eye (epicanthic fold) and preauricular pits are common. An underdeveloped middle phalanx of the fifth finger, abnormal palmar flexion creases (epidermal flexural lines present on the hand's palmar surface), and kidney diseases develop. In females, defective development of ovaries leads to failure in developing secondary sexual characteristics and infertility.
Complete Trisomy 22: It is a severe condition where three copies of the chromosome are present in every body cell. The disease always leads to miscarriages. There is no chance for the baby's survival as the disorder is incompatible with life development. The fetuses develop intrauterine growth retardation with multi-systematic defects like abnormal extremities, cardiovascular defects, brain malformations, and genitourinary systems.
Partial Trisomy 22: Partial trisomy 22 is often associated with cat eye syndrome, where variable features of congenital anomalies are present. The disorder develops due to interstitial duplication of chromosome 22. The most frequent presenting features are ocular coloboma (part of the tissue that makes the eye missing), preauricular pits or tags, anal anomalies, congenital heart, and renal malformations. In addition, craniofacial malformation, skeletal anomalies, and mental retardation may occur.
What Are the Clinical Characteristics of Trisomy 22?
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Facial malformation includes an underdeveloped midface, flat or broad nasal bridge, drooping eyes, wide-spaced (hypertelorism), epicanthic folds, and malformed ears with pits or tags.
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Microcephaly (baby's head is smaller than expected).
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Cranial abnormalities.
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Congenital heart disease and structural and functional anomalies of the heart.
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Genital abnormalities like delayed puberty and underdevelopment of secondary sexual characteristics.
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Intrauterine growth restriction.
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Anal atresia is a congenital abnormality with no opening at the end of the digestive tract where the anus is present.
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Hypospadias (congenital malformation of male external genitalia).
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Delayed growth and body asymmetry due to unequal development.
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Pigmented moles or birthmarks.
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Poor and abnormal nail development.
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Webbed necks.
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Unilateral hearing impairment.
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Intellectual deficiency.
How to Diagnose Trisomy 22?
A complete physical examination, medical history, and family history are necessary. Prenatal diagnosis for trisomy 22 with specialized tests like ultrasound and amniocentesis is essential. Fetal ultrasound is a non-invasive test that uses high-frequency waves to produce fetal images. Further testing with amniocentesis or chorionic villi sampling (a test to detect genetic defects) is recommended if any abnormality is detected. During amniocentesis, a sample of amniotic fluid is taken for analysis. Chromosomal typing of amniotic fluid is helpful for the identification of trisomy 22. The diagnosis is confirmed by fetal blood sampling or fetal skin biopsy.
After birth, trisomy is confirmed by clinical characteristic assessment and chromosomal analysis. Specific tests for various developmental defects like cardiovascular, hearing impairment, renal abnormality, and ovarian dysgenesis are essential for diagnosis and management. In complete trisomy 22, genetic testing after miscarriage or stillbirth is carried out.
Evaluation of vision, hearing, kidneys, central nervous system, genitalia, heart defects, and the immune system is necessary. Laboratory tests must be performed to determine electrolyte levels, serum calcium levels, thyroid function tests, kidney function tests, urine tests, and sex hormone studies. Radiological examination of brain scans, CT (computed tomography), and MRI (magnetic resonance imaging) may be necessary.
How to Treat Trisomy 22?
In milder trisomy, the treatment depends on specific problems individuals develop. The treatment often requires a multidisciplinary approach requiring various specialties. A surgical approach is necessary for patients with congenital cardiac defects and craniofacial and physical abnormalities. The surgical procedures depend on the anomaly's severity, symptoms, and other factors. Hearing loss is treated with prostheses like specialized hearing aids. Earlier intervention can improve the affected individual's quality of life. Additional help like speech therapy, physical therapy, and medical, social, or vocational services may be necessary to improve the patient's health.
What Are the Complications Associated With Trisomy 22 Syndrome?
Parents and caregivers may face severe emotional stress. Infants born with the disease experience failure to thrive, delayed milestone achievement, infertility, kidney malformation, and cardiomyopathy. The affected child faced ostracism (exclusion from society or a group) from society and reduced quality of life.
Conclusion
Trisomy 22 is a chromosomal disease with an extra chromosome in a few or most body cells. The severity of symptoms varies depending on the percentage of cells associated with the disease. The condition might be one of the causes of spontaneous abortion during the first trimester. Most fetuses that develop trisomy 22 do not get past the first trimester. The disease has no specific cure, and the symptoms are managed with treatment.
