Abstract

Case Report

A Rare Consanguineous Case of Alazami Syndrome in a Jordanian Family: Clinical Presentation, Genetic Analysis, and Therapeutic Approaches - A Case Report

Fawzi Irshaid*, Salim Alawneh, Qasim Al Souhail, Aisha Alshdefat, Bashar Irshaid and Ahmed Irshaid

Published: 07 May, 2024 | Volume 8 - Issue 1 | Pages: 003-006

Objective: Alazami syndrome (AS) is an infrequent genetic disorder inherited in an autosomal recessive pattern, characterized by the presence of multiple congenital abnormalities. This study explores a case of a 4-year-old girl with AS, examining symptoms, genetic factors, and treatment efficacy. 
Case report: A 4-year-old girl, born to consanguineous Jordanian parents, displayed dysmorphic features including low birth weight, microcephaly, hyperthyroidism, short stature, blue sclera, triangular-shaped face, deep-set eyes, narrow palpebral fissures, and a prominent forehead. Examination revealed height (92 cm) and weight (7.7 kg) below the 5th and 3rd percentiles respectively. Blood tests and renal ultrasound were normal. Whole exome sequencing (WES) identified a homozygous eight-base pair deletion within exon 5 of the LARP7 gene on chromosome 4q25, confirming the diagnosis of AS, an autosomal recessive disorder. This variant induces frameshift mutations leading to premature stop codons, suggesting a probable mechanism of illness via loss of function. Treatment involving growth monitoring and therapy led to significant improvements in height, weight, and communication skills within three months. 
Conclusion: We describe a rare autosomal recessive AS case due to consanguinity, with a frameshift mutation in the LARP7 gene found via WES. Our AS treatment program effectively alleviates symptoms and enhances developmental progress.

Read Full Article HTML DOI: 10.29328/journal.jcmei.1001031 Cite this Article Read Full Article PDF

Keywords:

Alazami syndrome; Consanguineous parents; Hyperthyroidism; LARP7 gene; Whole exome sequencing

References

  1. Alazami AM, Al-Owain M, Alzahrani F, Shuaib T, Al-Shamrani H, Al-Falki YH, Al-Qahtani SM, Alsheddi T, Colak D, Alkuraya FS. Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. Hum Mutat. 2012 Oct;33(10):1429-34. doi: 10.1002/humu.22175. Epub 2012 Aug 30. PMID: 22865833.
  2. Bajafar A, Rifai F, Al-Said Y, Cupler E. Alazami syndrome due to LARP7 gene mutation: Expanding the phenotype. Journal of the Neurological Sciences. 2019; 405: 272-273.
  3. Al-Hinai A, Al-Hashmi S, Ganesh A, Al-Hashmi N, Al-Saegh A, Al-Mamari W, Al-Murshedi F, Al-Thihli K, Al-Kindi A, Al-Maawali A. Further phenotypic delineation of Alazami syndrome. Am J Med Genet A. 2022 Aug;188(8):2485-2490. doi: 10.1002/ajmg.a.62778. Epub 2022 May 14. PMID: 35567578.
  4. Fauntleroy-Love KD, Wilson TE, Padem N, Golomb MR. 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. Child Neurol Open. 2023 Jul 27;10:2329048X231190784. doi: 10.1177/2329048X231190784. PMID: 37529055; PMCID: PMC10388622.
  5. Soengas-Gonda E, Pérez de la Fuente R, Arteche-López A, Gómez-Cano MLÁ, Quesada-Espinosa JF, Palma Milla C, Lezana Rosales JM, Mayo de Andrés S, Sánchez-Calvín MT, Gómez-Rodríguez MJ, Sierra Tomillo O, Juarez Rufian A, Ramos Gomez P, Herrero-Forte C, Fenollar-Cortés M, Cotarelo-Pérez C, García Ron A, Pérez Rodríguez O, Oancea-Ionescu R, Moreno-García M. Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families. Neuropediatrics. 2023 Feb;54(1):31-36. doi: 10.1055/a-1947-8411. Epub 2022 Sep 20. PMID: 36126956.
  6. Ling TT, Sorrentino S. Compound heterozygous variants in the LARP7 gene as a cause of Alazami syndrome in a Caucasian female with significant failure to thrive, short stature, and developmental disability. Am J Med Genet A. 2016 Jan;170A(1):217-9. doi: 10.1002/ajmg.a.37396. Epub 2015 Sep 16. PMID: 26374271.
  7. Dateki S, Kitajima T, Kihara T, Watanabe S, Yoshiura KI, Moriuchi H. Novel compound heterozygous variants in the LARP7gene in a patient with Alazami syndrome. Hum Genome Var. 2018 Mar 29;5:18014. doi: 10.1038/hgv.2018.14. PMID: 29619239; PMCID: PMC5874394.
  8. Hasler D, Meduri R, Bąk M, Lehmann G, Heizinger L, Wang X, Li ZT, Sement FM, Bruckmann A, Dock-Bregeon AC, Merkl R, Kalb R, Grauer E, Kunstmann E, Zavolan M, Liu MF, Fischer U, Meister G. The Alazami Syndrome-Associated Protein LARP7 Guides U6 Small Nuclear RNA Modification and Contributes to Splicing Robustness. Mol Cell. 2020 Mar 5;77(5):1014-1031.e13. doi: 10.1016/j.molcel.2020.01.001. Epub 2020 Feb 3. PMID: 32017898.
  9. Imbert-Bouteille M, Mau Them FT, Thevenon J, Guignard T, Gatinois V, Riviere JB, Boland A, Meyer V, Deleuze JF, Sanchez E, Apparailly F, Geneviève D, Willems M. LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters. Eur J Med Genet. 2019 Mar;62(3):161-166. doi: 10.1016/j.ejmg.2018.07.003. Epub 2018 Jul 10. PMID: 30006060.
  10. Wojcik MH, Linnea K, Stoler JM, Rappaport L. Updating the neurodevelopmental profile of Alazami syndrome: Illustrating the role of developmental assessment in rare genetic disorders. Am J Med Genet A. 2019 Aug;179(8):1565-1569. doi: 10.1002/ajmg.a.61189. Epub 2019 May 10. PMID: 31074943; PMCID: PMC6663627.
  11. Amberger J, Bocchini C, Hamosh A. A new face and new challenges for Online Mendelian Inheritance in Man (OMIM®). Hum Mutat. 2011 May;32(5):564-7. doi: 10.1002/humu.21466. Epub 2011 Apr 5. PMID: 21472891.
  12. Durkie M, Cassidy E-J, Ian Berry I, Owens M, Turnbull C, Scott RH, Taylor RW, Deans ZC, Ellard S, Baple EL, Dominic J McMullan DJ. ACGS Best Practice Guidelines for Variant Classification in Rare Disease 2024. Recommendations ratified by The Association for Clinical Genomic Science (ACGS) Quality Subcommittee on 20th February 2024. https://www.acgs.uk.com/media/12533/uk-practice-guidelines-for-variant-classification-v12-2 024. pdf.
  13. Cheng L, Zhao H, Wang P, Zhou W, Luo M, Li T, Han J, Liu S, Jiang Q. Computational Methods for Identifying Similar Diseases. Mol Ther Nucleic Acids. 2019 Dec 6;18:590-604. doi: 10.1016/j.omtn.2019.09.019. Epub 2019 Sep 28. PMID: 31678735; PMCID: PMC6838934.
  14. Woodward AA, Urbanowicz RJ, Naj AC, Moore JH. Genetic heterogeneity: Challenges, impacts, and methods through an associative lens. Genet Epidemiol. 2022 Dec;46(8):555-571. doi: 10.1002/gepi.22497. Epub 2022 Aug 4. PMID: 35924480; PMCID: PMC9669229.
  15. Wojcik MH, Linnea K, Stoler JM, Rappaport L. Updating the neurodevelopmental profile of Alazami syndrome: Illustrating the role of developmental assessment in rare genetic disorders. Am J Med Genet A. 2019 Aug;179(8):1565-1569. doi: 10.1002/ajmg.a.61189. Epub 2019 May 10. PMID: 31074943; PMCID: PMC6663627.
  16. Meyer S, Yeh EA, Brunner J, Semler O, Gropman A. Editorial: New Therapeutic Options for Rare Diseases. Front Pediatr. 2022 Jan 24;9:832395. doi: 10.3389/fped.2021.832395. PMID: 35141184; PMCID: PMC8820370.

Figures:

Similar Articles

Recently Viewed

  • Environmental Factors Affecting the Concentration of DNA in Blood and Saliva Stains: A Review
    Divya Khorwal*, GK Mathur, Umema Ahmed and SS Daga Divya Khorwal*, GK Mathur, Umema Ahmed, SS Daga. Environmental Factors Affecting the Concentration of DNA in Blood and Saliva Stains: A Review. J Forensic Sci Res. 2024: doi: 10.29328/journal.jfsr.1001057; 8: 009-015
  • Why Down-managing Backlog Forensic DNA Case Entries Matters
    JH Smith* and JS Horne JH Smith*, JS Horne. Why Down-managing Backlog Forensic DNA Case Entries Matters. J Forensic Sci Res. 2024: doi: 10.29328/journal.jfsr.1001056; 8: 001-008
  • Scintigraphic non-invasive diagnosis of amyloid cardiomyopathy
    Laroussi Mohamed-Salem*, Tomás E Rodríguez-Locarno, Tatiana Moreno-Monsalve, Isabel Castellón-Sánchez, José F Contreras-Gutiérrez and Antonia Claver-Valderas Laroussi Mohamed-Salem*,Tomás E Rodríguez-Locarno,Tatiana Moreno-Monsalve,Isabel Castellón-Sánchez,José F Contreras-Gutiérrez ,Antonia Claver-Valderas. Scintigraphic non-invasive diagnosis of amyloid cardiomyopathy. J Cardiol Cardiovasc Med. 2019: doi: 10.29328/journal.jccm.1001058; 4: 156-158
  • Anomalies of coronary artery origin: About two cases
    Dioum M*, Sarr EM, Manga S, Mingou JS, Diack A, Diop AD, Bindia D, Diagne PA, Sarr AN and Diop IB Dioum M*,Sarr EM,Manga S,Mingou JS,Diack A,Diop AD,Bindia D,Diagne PA,Sarr AN,Diop IB. Anomalies of coronary artery origin: About two cases. J Cardiol Cardiovasc Med. 2019: doi: 10.29328/journal.jccm.1001051; 4: 117-119
  • Late discover of a traumatic cardiac injury: Case report
    Benlafqih C, Bouhdadi H*, Bakkali A, Rhissassi J, Sayah R and Laaroussi M Benlafqih C,Bouhdadi H*,Bakkali A,Rhissassi J,Sayah R,Laaroussi M. Late discover of a traumatic cardiac injury: Case report. J Cardiol Cardiovasc Med. 2019: doi: 10.29328/journal.jccm.1001048; 4: 100-102

Read More

Most Viewed

Read More

Help ?