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

Brain Dev. 2021 Feb;43(2):337-342. doi: 10.1016/j.braindev.2020.09.007. Epub 2020 Oct 12.

Abstract

Background: 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.

Case report: 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.

Discussion: 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.

Keywords: Corpus callosum dysgenesis; Immunodeficiency; Microcephalic osteodysplastic primordial dwarfism type I (MOPD I); Pachygyria; RNU4ATAC; Roifman syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Alleles
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / physiopathology
  • Dwarfism / genetics*
  • Dwarfism / physiopathology
  • Exome Sequencing
  • Female
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / physiopathology
  • Humans
  • Microcephaly / genetics*
  • Microcephaly / physiopathology
  • Mutation
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / physiopathology
  • Pedigree
  • Phenotype
  • Primary Immunodeficiency Diseases / genetics*
  • Primary Immunodeficiency Diseases / physiopathology
  • RNA, Small Nuclear / genetics*
  • Retinal Diseases / genetics*
  • Retinal Diseases / physiopathology
  • X-Linked Intellectual Disability / genetics*
  • X-Linked Intellectual Disability / physiopathology

Substances

  • RNA, Small Nuclear
  • RNU4ATAC RNA, human

Supplementary concepts

  • Microcephalic osteodysplastic primordial dwarfism, type 1
  • Roifman syndrome