Phenotypic Variations of Cartilage Hair Hypoplasia: Granulomatous Skin Inflammation and Severe T Cell Immunodeficiency as Initial Clinical Presentation in Otherwise Well Child with Short Stature

Abstract

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/ or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.

Successful long‐term outcome after combined hematopoietic stem cell transplantation and small bowel transplantation: A case report and review of the literature

“…CHH is a rare autosomal recessive skeletal dysplasia, with phenotypic heterogeneity and manifestations including varying degrees of immunodeficiency, disproportionate short stature, an increased risk of malignancies, and fine sparse hair. Gastrointestinal anomalies also vary, ranging from HD limited to the rectosigmoid to total colonic aganglionosis …”

“…Gastrointestinal anomalies also vary, ranging from HD limited to the rectosigmoid to total colonic aganglionosis. 11 The immunodeficiency in CHH is primarily a CD4 and CD8 lymphocytopenia, but humoral immunity may also be affected with IgA and IgG subclasses being the most common. 12 Severe combined immunodeficiency in the setting of CHH should be evaluated for HSCT as early as possible, as patients generally do not survive beyond the first year of life without immune reconstitution with HSCT.…”

Pregnancy Outcome in Cartilage-Hair Hypoplasia, a Rare Form of Dwarfism

“…Cartilage-hair hypoplasia (CHH) is a rare form of short-limbed dwarfism with an incidence of 1/23,000 births [ 7 ]. It is the result of a genetic autosomal recessive pattern of inheritance, from a mutation to the noncoding RNA gene, RMRP [ 8 ]. The RMRP mutation disrupts ribosomal processing and progression through the cell cycle in rapidly dividing cells, such as chondrocytes [ 8 ], which results in defective cell proliferation [ 7 ].…”

“…It is the result of a genetic autosomal recessive pattern of inheritance, from a mutation to the noncoding RNA gene, RMRP [ 8 ]. The RMRP mutation disrupts ribosomal processing and progression through the cell cycle in rapidly dividing cells, such as chondrocytes [ 8 ], which results in defective cell proliferation [ 7 ]. Cartilage deficiency at the metaphyseal ends of bones causes shortening of limbs [ 8 ].…”

“…The RMRP mutation disrupts ribosomal processing and progression through the cell cycle in rapidly dividing cells, such as chondrocytes [ 8 ], which results in defective cell proliferation [ 7 ]. Cartilage deficiency at the metaphyseal ends of bones causes shortening of limbs [ 8 ]. Similar disruption to lymphocytes can result in defective proliferation of T lymphocytes, causing features of severe T cell immunodeficiency [ 8 ].…”