P3.S370: Neuronal migration defects and infantile spasms in mosaic partial tetrasomy of chromosome 3q

Introduction: Published features of tetrasomy of chromosome 3q include hirsutism, dysmorphisms, developmental delays, and structural heart abnormalities. Infantile spasms have not been previously described. We present a patient with mosaic partial tetrasomy of chromosome 3q with stenogyria who developed infantile spasms at 6 months of life. Both prenatal surgical correction of spina bifida and infantile spasms required medical transport due to lack of highly specialized care on Oahu.

Case Description: An amniocentesis at 21 weeks at Tripler Army Medical Center (TAMC) in Honolulu, HI revealed 3q26.32q29 and fetal MRI demonstrated spinal myelomeningocele, Chiari II malformation, and mild ventriculomegaly. The mother of patient was transported to Huntington Medical Center in Pasadena, CA for in utero spina bifida repair at 25 weeks. MRI on day of life 2 at Children’s Hospital Los Angeles showed stenogyria. After discharge from the NICU, the patient returned to Honolulu. At 11 weeks of life, the patient developed focal clinical seizures. EEG was encephalopathic with left focal discharges. EEG 1 week later showed hypsarrhythmia. The patient had no history of clinical spasms up to this point. Keppra and phenobarbital were ineffective at controlling seizures. At 5 months of life, clear clinical infantile spasms emerged, and prednisolone achieved a satisfactory response. Due to anticipated medication refractory seizures and need for a pediatric epileptologist, the patient was relocated to Virginia Commonwealth University Medical Center in Richmond, VA.

Discussion: This is the first published case of infantile spasms in partial tetrasomy of chromosome 3q. Infantile spasms are associated with high morbidity and severe developmental disabilities. All modifiable prognostic factors involve early initiation of treatment. Awareness of the association between infantile spasms and tetrasomy of chromosome 3q may enable early recognition and treatment. In this patient, the neuronal migration defects identified at birth predicted development of medication refractory epilepsy. All branches of the U.S. military have programs in place to enable temporary duty travel, medical evacuation, or duty reassignment based on current medical needs. In this patient, development of infantile spasms and the expectation of medication resistant epilepsy prompted early reassignment of duty.

Conclusion: Tetrasomy of chromosome 3q is a rare condition and this report establishes that neuronal migration defects and epileptic encephalopathy, specifically infantile spasms, can be seen in this condition. While knowledge of clinical features of an obscure genetic condition may seem specious, this case illustrates relevance of this information when planning for future treatment, specifically in a military context. The mechanism for placement of medically complex military families to appropriate duty stations is mainly based on current medical needs. This case highlights how knowledge of the natural progression of a disease course can and should affect duty assignment decisions to enable appropriate medical care.