The burgeoning utility of microarray-based comparative genomic hybridization has led to the characterization of a novel 4q21 microdeletion syndrome.  The literature to date reports several major features common to patients with 4q21 microdeletion syndrome including neonatal muscular hypotonia, severe psychomotor retardation, marked progressive growth restriction, absent or severely delayed speech and distinctive facial features. We describe the phenotypic features of a patient found to have a de-novo 3.4 Mb deletion at 4q21.21 to 4q21.23 including a unique finding not previously reported in patients with 4q21 microdeletion syndrome. The patient is a 2 year old male that was born at 34 weeks and was initially seen in the neonatal intensive care unit for severe micrognathia, u-shaped cleft palate and posterior displacement of the tongue.  He underwent surgeries for mandibular distraction and cleft palate repair, as well as bilateral orchiopexies for undescended testes. He is followed by Cardiology for a restrictive atrial septal defect, without evidence of a significant degree of right atrial or right ventricular volume enlargement. Upon physical exam at 2 years of age, his height and weight were below the 3rd percentile and head circumference was between 10-25th percentiles. Facial features include thin lips, long palpebral fissures, long philtrum and small hands and feet. He is receiving multiple therapy services through the Early Intervention program and his delays in development are significant.  He does not walk and has limited speech.   Oligonucleotide microarray performed at 2 years of age revealed a de-novo 3.4 Mb deletion at 4q21.21q21.23 (ch4:82048194-85469787). Published array data on individuals with 4q microdeletion syndrome identified overlapping 4q21 deletions of various sizes (3.2-15.1Mb).  The array finding identified in our patient is one of the smaller deletions reported in the 4q21 microdeletion syndrome but does overlap with other reported deletions. A review of the published literature did not reveal any previous reported cases of patients with 4q21 microdeletion syndrome having cleft palate and/or Pierre Robin sequence.  As less than 20 patients have been described in the literature with 4q21 microdeletion syndrome, cleft palate and Pierre Robin sequence may represent a finding of this newly described syndrome that has not been previously observed.  Our patient contributes to the phenotypic spectrum of the 4q21 microdeletion syndrome.  Detailed examination of the palate of patients with 4q21 microdeletion syndrome is warranted.  

This poster (#226) will be presented at the ACMG Annual Meeting by Chris Tan, our genetic counselor, Friday March 30: 10:30-11:30 am. Stop by and learn more