Pathophysiology
As the name chromosome 22q11.2 deletion syndrome implies, the syndrome is the result of a 2-3 million base pair (Mb) deletion on the long arm of chromosome 22. This area is prone to microdeletion because of the presence of nonallelic, flanking, low-copy repeat DNA sequences in the region, which lead to unequal crossing over between the two chromosome 22s during meiosis.
As the name chromosome 22q11.2 deletion syndrome implies, the syndrome is the result of a 2-3 million base pair (Mb) deletion on the long arm of chromosome 22. This area is prone to microdeletion because of the presence of nonallelic, flanking, low-copy repeat DNA sequences in the region, which lead to unequal crossing over between the two chromosome 22s during meiosis.
Frequency
Estimates of the incidence of chromosome 22q11.2 deletion syndrome range from 1 per 2000-4000 in the general population. It is a frequent cause of cleft palate and congenital heart defects.
Estimates of the incidence of chromosome 22q11.2 deletion syndrome range from 1 per 2000-4000 in the general population. It is a frequent cause of cleft palate and congenital heart defects.
Sex
Males and females appear to be equally affected.
Age
This is a congenital condition, but age at diagnosis largely depends on the severity and the types of birth defects. Thus, those with more serious cardiac defects, hypocalcemia, or both observed in classic DGS are diagnosed in the neonatal period. Recurrent infections usually present in patients older than 3-6 months. Some individuals without hypocalcemia who have normal immune function, mild cardiac defects, and minimal facial anomalies may not be diagnosed until late childhood. Late diagnosis into adulthood continues to be reported, especially in those with isolated mild symptoms. Diagnosis in fetuses with a congenital heart anomaly should be offered to the pregnant woman.
Clinical Features
Patients usually have characteristic facies, which become more pronounced as the children grow into the second decade. These are often recognized in white children and consist of a high and broad nasal bridge, long face, narrow palpebral fissures, and micrognathia. Microcephaly and asymmetric crying face may be present.
Males and females appear to be equally affected.
Age
This is a congenital condition, but age at diagnosis largely depends on the severity and the types of birth defects. Thus, those with more serious cardiac defects, hypocalcemia, or both observed in classic DGS are diagnosed in the neonatal period. Recurrent infections usually present in patients older than 3-6 months. Some individuals without hypocalcemia who have normal immune function, mild cardiac defects, and minimal facial anomalies may not be diagnosed until late childhood. Late diagnosis into adulthood continues to be reported, especially in those with isolated mild symptoms. Diagnosis in fetuses with a congenital heart anomaly should be offered to the pregnant woman.
Clinical Features
Patients usually have characteristic facies, which become more pronounced as the children grow into the second decade. These are often recognized in white children and consist of a high and broad nasal bridge, long face, narrow palpebral fissures, and micrognathia. Microcephaly and asymmetric crying face may be present.
- The most common malformation in this region is cleft of secondary palate. Submucous cleft palate or velopharyngeal incompetence (VPI) without a cleft may be present. Approximately 27% of patients have VPI.
- Poor sucking and nasal regurgitation due to VPI or a submucous cleft palate may be present.
- The swallowing problem usually resolves by the end of the first year, leaving the child with hypernasal speech as the major remaining manifestation.
- Recurrent episodes of otitis media may be observed. Conductive or sensorineural hearing loss (or both) may be present.
- Recurrent infections secondary to immune deficiency may be observed.
- Hypocalcemia due to hypoparathyroidism can cause seizures.
- Developmental delay and learning difficulties are observed in 70-90% of patients.
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