DiGeorge Syndrome

Patient Presentation:
K.S. is an 18 month old male who presented to the pediatric clinic for a well-child visit.  His mother voiced concern that he was significantly delayed in achieving both verbal and motor developmental milestones.  K.S. had only recently begun walking unassisted.  He was not yet pointing to indicate wants or waving.  “Mama” and “Dada” were the only recognizable words he used although he did babble.  K.S.’s mother also reported concern regarding his height and weight, both of which were below the 5th percentile on the CDC growth curve.   Past medical history was significant for low birth weight, presence at birth of a small VSD which spontaneously resolved by 4 months of age, penile chordee without hypospadias which was surgically corrected at 11 months and frequent respiratory infections and high fevers as an infant.  Upon physical exam, some mild dysmorphic features were noted including micrognathia, fused lower lateral and central incisors, a left preauricular skin tag and bilateral fifth finger clinodactyly. The child appeared small and thin but well cared for, with no signs of neglect or abuse.   K.S.’s mother reported that he had a good appetite and ate a variety of foods from all food groups.   The patient’s mother was 5’6” and father was 6’4”.   The patient’s family history was negative for genetic disorders.

Differential List:
Laboratory tests: CBC-WNL, CMP-WNL, Sweat electrolytes  test- 25mEq/L (normal finding, not indicative of cystic fibrosis)
Normal XY karyotype
Array based comparative genomic hybridization (aCGH) confirmed at least 970kb deletion at 22q11.2. This is a test that is used to detect changes in a chromosome such as deletions or duplications of material.  It is used when physical findings indicate likely chromosomal abnormalities. 
Radiographic studies: Renal ultrasound showed malrotation of left kidney thought to be a variant of normal
Hearing and vision tests: normal

DiGeorge  syndrome is one of a number of disorders including velocardiofacial syndrome, and conotruncal anomaly face syndrome caused by a partial deletion of the long arm of the 22nd chromosome (22q11.2).  Because the phenotypes associated with these syndromes can vary widely, they were once thought to be distinct disorders.  Following the discovery that all are caused by the same genetic error; a movement began to reclassify all of the known syndromes associates with the 22q deletion as 22q11.2 deletion syndrome.  Although there are a large number of abnormalities linked to the 22q11.2 deletion, some characteristic findings include: immune system deficits (often only seen in infancy), hypocalcemia (sometimes resulting in seizures),  short stature, skeletal abnormalities, renal abnormalities, heart defects, cleft palate, developmental delays,  learning disorders  and ADHD.  Individuals with 22q11.2 deletions are also at significantly higher risk for developing schizophrenia as adults than those without the deletion.

There is no treatment for the chromosomal deletion that causes DiGeorge syndrome.  A treatment plan is tailored to the individual patient’s symptoms.  Following his diagnosis, K.S. began physical, occupational, and speech therapy to address his developmental delays.  He was also started on a high calorie diet to address his low weight.   

K.S. is now 10 years old and is working at grade level in a mainstream fourth grade classroom.  He continued to receive speech, physical, and occupational therapy until that age of 7 when those services were discontinued due to his significant progress.  At age 7 K.S. was diagnosed with ADHD and started on a stimulant medication with good results.  K.S. remains small for his age with both height and weight falling between the 10th and 25th percentiles.

Case created by Karen Sanchez, 2012.