Further phenotypic delineation of Alazami syndrome

Abstract

Alazami syndrome (AS) is an autosomal recessive condition characterized by the cardinal features of severe growth restriction, moderate to severe intellectual disability, and distinctive facial features. Biallelic pathogenic variants of the LARP7, encoding a chaperone of 7SK noncoding RNA, is implicated in this disease. There are <35 reported cases in the literature. All reported cases share the same three cardinal features of the syndrome. Herein, we report on 12 patients with a confirmed diagnosis of AS from eight unrelated families. The cohort shares the same key feature of the syndrome. Moreover, we report additional phenotypic features, including genitorenal anomalies, ophthalmological abnormalities, and congenital heart disease.Whole-exome sequencing was used in all reported cases, implicating a clinical underrecognition of the syndrome. This report further expands the clinical and molecular characteristics of Alazami syndrome.

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

“…Facial and other physical features: Our patient had lessfrequently reported features including hypertelorism, syndactyly and overlapping toes, strabismus and thickened skin have also been reported in Alazami our patient did not have these. 1,6,13,[15][16][17][18][19] Hematological and immunological findings: Our patient had TEC, a self-limiting red cell aplasia which may be triggered by infection, but appears to have a genetic component. 20 One case of TEC and several cases of borderline anemia have been reported in Alazami Syndrome.…”

“…Feeding issues: Our patient had ongoing feeding issues; similar problems occurred in 6 other patients. 1,14,17,18 Hearing loss: Our patient had hearing loss possibly due to ear infections, issues with tympanostomy tubes and meningitis, possibly related to his immunological issues, Another Alazami patient with mild conductive hearing loss has been described. 16 Sleep disorders: Our patient had sleep apnea; this has been reported in another Alazami patient.…”

“…Facial and other physical features: Our patient had less-frequently reported features including hypertelorism, syndactyly and overlapping toes, strabismus and thickened skin have also been reported in Alazami our patient did not have these. 1 , 6 , 13 , 15 – 19 …”

“…Brain malformations have been described in a few children with Alazami, but several papers in the Alazami literature do not report brain MRIs. Of the documented MRIs, findings included normal exam, unilateral mild insular and anterior frontal gyrus cortical thickening, 3 , 17 increased signal in periventricular white matter, 4 corpus callosum agenesis and absence of septum pellucidum, 15 thin corpus callosum and disorganized cerebellar hemispheres, 1 Arnold Chiari malformation type 1, venous angioma, 25 and mild myelination delay. 26 LARP7 is most highly expressed in the brain.…”

Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families

“…To the best of our knowledge, less than 50 patients have been reported until now, [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] including the first 10 patients from a consanguineous Saudi Arabian family in whom the syndrome was described 5 (►Supplementary Table S1, available in the online version).…”