SUN-290 Responsiveness of Growth Hormone Therapy in a Patient with Complex Chromosome 4 q Interstitial Deletion

Background Information: Chromosome 4 q interstitial deletion is a rare chromosomal disorder characterized by post natal growth retardation, developmental delay, craniofacial dysmorphism and behavioral problems. Not only are the characteristics of growth failure in these patients ill defined, but their responsiveness to growth hormone (GH) treatment is also lacking in the literature. An index case of a 7 year old male with unique interstitial deletion of chromosome 4 q deletion at q13.3 and q22.12 with a normal segment in between presented with significant growth failure in early infancy and was treated with growth hormone as described below. Case Report: He was born at 36 weeks gestation with a birth weight of 4 pounds 6 ounces (3(rd) percentile) and a birth length of 19 inches (50(th) percentile). Pregnancy was complicated by oligohydraminos. Post natal course was complicated by feeding difficulties and jaundice. He grew along the 5(th) percentile till age 6 months and then started faltering off below the 3(rd) percentile in both height and weight. He was started on dense caloric formula but his growth parameters continued to decline. His intake was reported good and had no diarrhea or vomiting. A TFT obtained demonstrated a slightly elevated TSH of 9.4 mcIU/ml (reference range 0.4-9.2) and marginally low Free T4 of 0.76 ng/dl (reference range 0.89-1.48). He was started on a small dose of 12.50 mcg thyroxin daily which did not improve his growth (thyroxin was discontinued at age 4 ½ year). His chemistry panel, IGF-1 and IGFBP-3 obtained were all normal. A bone age was concordant with his chronological age. Karyotype was 46 XY. Comparative genomic hybridization (CGH) array revealed a de novo 2.2 Mb deletion at 4q 13.3 and 2.2 Mb deletion at 4q22.1-q22.3. Deletions were separated by 18.3 Mb of normal copy number sequence. Other tests obtained demonstrated a normal pituitary gland on brain MRI and no tethered cord on the spinal MRI. He was started on GH for small for gestational age indication at age 13 month. His height and weight percentile improved significantly from <1% at age 13 month to 5(th)% by age 2 year and has continued to grow along 10-12 % since age 4 year. His other associated medical problems include improving developmental delay (attends special class with IEP and speech therapy), sleep disturbances (on melatonin and clonidine), mild hypotonia (received OT and PT, now resolved), poor dental enamel (has needed 8 crowns), obstructive sleep apnea with high arched palate (status post turbinate reduction and CPAP), clinodactyly, hyperopia with astigmatism (wears glasses) and sacral dimple. His behavior problems include high anxiety and obsessive/perseveration behavior. Conclusions: Growth failure is a characteristic feature in patients with chromosome 4 q deletion. These patients with growth retardation when treated with GH may respond with improved growth velocity and weight gain and hence should be considered.