Introduction • There are a variety of physical and behavioral disorders

that have been linked to 22q11.2 deletion syndrome. The syndrome has the potential to impact every system in the body and can therefore lead to a wide-range of health issues.

• We present the first known case of a neonate with confirmed diagnosis of 22q11.2 deletion syndrome with congenital eventration of the diaphragm.

A Case of 22q11.2 Deletion Syndrome with Congenital Eventration of the Diaphragm

Marvi Montano MD PGY-2, Ma Teresa Ambat MD, Ferdinand Shamiyeh MD PGY-1, Garrett Levin MDTexas Tech University Health Sciences Center-Paul L Foster School of Medicine, El Paso, Texas

Discussion – 22q11.2 Deletion Synonyms: DiGeorge Syndrome, Velocardiofacial Syndrome (VCFS), Conotruncal Anomaly Face Syndrome, Autosomal Dominant Opitz G/BBB Syndrome, Sedlackova Syndrome, Cayler Cardiofacial.

Disease characteristics. Individuals with 22q11.2 deletion syndrome (22q11.2DS) have a wide range of findings including the following:•Congenital heart disease (74%), specifically conotruncal malformations as seen in our patient (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus). •Palatal abnormalities (69%), particularly velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate. •Patients often have characteristic facial characteristics, and learning difficulties (70%-90%). •Most patients also have an immune deficiency (regardless of the clinical presentation, 77%).

Additional findings. Numerous patients also manifest with: •Hypocalcemia (50%), significant feeding and swallowing problems; constipation + structural gastrointestinal anomalies, renal anomalies (31%), hearing loss, laryngotracheoesophageal anomalies, growth hormone deficiency, autoimmune disorders, seizures, CNS anomalies, skeletal abnormalities, ophthalmologic abnormalities, enamel hypoplasia, and rarely malignancies. •Developmental delay ( particular delays in emergence of language), intellectual disability, and learning differences are common. Autism or autistic spectrum disorder is found in ~20% of children and psychiatric illness (specifically schizophrenia) is present in 25% of adults.

Diagnostic Testing. 22q11.2 deletion syndrome is diagnosed in children with a submicroscopic deletion of chromosome 22 detected by fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), or chromosomal microarray (CMA).

The majority of affected individuals (85%) have a large (3-Mb) deletion encompassing approximately 40 genes; a subset of individuals have a smaller atypical or ‘‘nested’’ deletion. 

Management. Multidisciplinary team tailored to the affected child’s specific needs. Calcium supplementation and referral to an endocrinologist for hypocalcemia and thyroid monitoring; treatment for GERD and gastrointestinal dysmotility for feeding difficulties; educational intervention and speech therapy. Immune deficiency necessitates aggressive treatment of infections; rarely, prophylactic antibiotics, IVIG, or thymic transplantation are indicated. Early diagnosis and intervention for psychiatric illnesses improve the long-term prognosis and quality of life.

Long-term prognosis: Prognosis depends on the degree of involvement of the multiple organ systems. Majority will survive and grow into adulthood with the proper treatment of heart defects, immune system disorders, and other health problems. Patients with 22q11.2 DS will generally need extra help throughout school and will need long term care for their individual health needs

• A 2,410-g male, 38 weeks’ gestation was born small

for gestational age to a 25-year-old primigravida woman after an uncomplicated pregnancy.

• On examination, the infant appeared in no distress. His weight, length and head circumference were below the third percentile. Further examination revealed mild differences in facial features with low-set ears and a loud murmur, the rest was unremarkable.

• He was admitted at age 2 hours to the NICU because of hypoglycemia. His NICU course and results of diagnostic evaluation were as follows:

• Sepsis evaluation due to recurrent hypoglycemia: Sepsis screen – negative. Empiric antibiotics discontinued after 2 days.

• Recurrent hypoglycemia: Resolved by day 9 and off TPN/IV fluids by day 14. Negative work-up (insulin, ammonia, lactate, serum ketones, cortisol, fT4 and TSH)

• Murmur: Cardiac echo revealed Tetralogy of Fallot. Emergent surgery not required.

• Genetics: Finding of TOF (a conotruncal defect) and mild dysmorphic facial features prompted karyotype and FISH for DGCR. FISH confirmed 22q11.2 DS.

• Hypocalcemia: Transient hypocalcemia on day 3 recurred on day 13 causing focal seizures which responded well to calcium supplementation.

• Additional testing after confirmation of 22q11.2 DS: Renal US – normal. Head US – normal. IgA and IgE levels – borderline low. TREC – T cell number ~ 2/3 normal value. Flow cytometry – not definitive.

• New onset desaturations on day 15: Chest x-ray showed persistent density at the right lower lobe which proved to be an eventration of right hemidiaphragm on chest MRI. Plain radiograph of the chest and MRI are shown below.

• Disposition: He was discharged in stable condition on calcium glubionate supplementation and PM 60/40. Multi-subspecialty follow-up arranged for close surveillance.

Conclusions

References

2013 Texas Pediatric Society Electronic Poster Contest

 

• Clinical suspicion of 22q11.2 DS rises when a neonate presents with heart defects, hypocalcemia and characteristic facial features. We presented a case of 22q11.2 DS with TOF, hypoparathyroidism-hypocalcemia, mildly decreased T-cell number, mild hypogammaglobulinemia and subtle dysmorphic facial features.

• The incidental finding of congenital eventration of the right hemidiaphragm is unique to this case and is probably the first to be reported. The recurrent hypoglycemia may have been due to his growth restriction, findings not previously reported in association with 22q11.2 DS.

• He will require surgical intervention for correction of the TOF and evaluation for respiratory compromise due to the eventration. He will continue to require calcium supplementation and close monitoring for severe infections. Surveillance for delays in learning and development, and in later life, for ADHD, schizophrenia, and depression is recommended.

1. McDonald-McGinn DM, Emanuel BS, Zackai EH. 22q11.2 Deletion Syndrome. GeneReviews. Initial posting; September 1999; Last update; February 2013

2. NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013

Objectives

• Recognize the clinical features of 22q11.2 DS leading to early identification and diagnosis in newborns

• Review the approach to treatment of 22q11.2 DS for prompt intervention and anticipation of potential complications

Case Summary

Figure 1: Chest radiography - No pulmonary congestion, suspect right lower lobe atelectasis.

Figure 2 Chest MRI: Soft tissue mass on the right lower lobe on CXR is found to be the liver. The liver extends to the lower lobe region of the chest. This region is felt to represent an eventration. No abnormal vasculature.