A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami

Abstract

Alazami syndrome is a rare autosomal recessive neurodevelopmental disorder due to loss-of-function variants in the La ribonucleoprotein 7 (LARP7) gene. Children with Alazami syndrome are most often affected by a combination of primordial dwarfism, intellectual disability, and distinctive facial features. Previous cases have been primarily found in consanguineous families from the Middle East, Asia, and North Africa. We present a 21-month-old Caucasian male from the Midwest United States with nonconsanguineous parents who presented with frequently reported findings of unusual facial features, poor growth, cardiac and genitourinary findings, and developmental delay; less-frequently reported findings, including transient erythroblastopenia of childhood (TEC) and immune deficiency; and never-before reported findings of periventricular nodular heterotopia and stroke. He developed stroke during a hospitalization for Hemophilus influenzae meningitis. The possible contributions of LARP7 to TEC, immune deficiency, brain malformation, and stroke are discussed. Guidelines for the care of Alazami patients are proposed.

Keywords: Alazami syndrome; LARP7; developmental disabilities; immune deficiency; intellectual disability; periventricular nodular heterotopia; primordial dwarfism; stroke; transient erythroblastemia of childhood.

Figure 1.

Physical features of an 18-month-old with Alazami syndrome. (A) Telecanthus (inner canthus outside the insertion of the nasal ala) and hypertelorism (pupils are aligned later to the outer corners of the mouth). (B) Overlapping toes on the right foot. (C) third digit brachydactyly on the left foot.

Figure 2.

Coronal T1 brain MRI demonstrating right periventricular nodular heterotopia (arrow).

Figure 3.

Diffusion-weighted brain MRI demonstrating 3.8 × 3 cm area of restricted diffusion in the left anterior frontal lobe involving the left anterior MCA territory.