Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome

• Published in: Brain & development (Tokyo. 1979) Vol. 43; no. 2; pp. 337 - 342
• Main Authors: Hagiwara, Hidetoshi, Matsumoto, Hiroshi, Uematsu, Kenji, Zaha, Kiyotaka, Sekinaka, Yujin, Miyake, Noriko, Matsumoto, Naomichi, Nonoyama, Shigeaki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021
• Subjects: Corpus callosum dysgenesis; Immunodeficiency; Microcephalic osteodysplastic primordial dwarfism type I (MOPD I); Pachygyria; RNU4ATAC; Roifman syndrome; Pachygyria; Roifman syndrome; Corpus callosum dysgenesis; RNU4ATAC; Immunodeficiency; Microcephalic osteodysplastic primordial dwarfism type I (MOPD I)
• ISSN: 0387-7604; 1872-7131; 1872-7131
• DOI: 10.1016/j.braindev.2020.09.007

Microcephalic osteodysplastic primordial dwarfism type I (MOPD I, also known as Taybi-Linder syndrome) is a rare genetic disorder associated with severe intrauterine growth retardation, short stature, microcephaly, brain anomalies, stunted limbs, and early mortality. RNU4ATAC, the gene responsible for this disorder, does not encode a protein but instead the U4atac small nuclear RNA (snRNA), a crucial component of the minor spliceosome. Roifman syndrome is an allelic disorder of MOPD I that is characterized by immunodeficiency complications. The patient described herein is an 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at the age of one, thereafter resulting in severe psychomotor disabilities. Genetic analysis using gene microarray and whole-exome sequencing could not identify the cause of her congenital anomalies. However, Sanger sequencing revealed a compound heterozygous mutation within RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity. Furthermore, antibodies against varicella-zoster, rubella, measles, mumps, and influenza were very low or negative despite having received vaccinations for these viruses. HHV-6 IgG antibodies were also undetected. The patient here exhibited a marked MOPD I phenotype complicated by various immunodeficiencies. Previous studies have not demonstrated immunodeficiency comorbidities within MOPD I subjects, but this report suggests an evident immunodeficiency in MOPD I. Patients with MOPD I should be treated with one of the immunodeficiency syndromes.