Understanding Cartilage Hair Hypoplasia
Cartilage hair hypoplasia (CHH) is a rare genetic condition categorized as a skeletal dysplasia. The term “hypoplasia” indicates underdevelopment. This condition primarily impacts the metaphysis, the wider part at the ends of long bones. Although CHH is a lifelong condition, affected individuals generally have normal intelligence and achieve typical developmental milestones during childhood.
Genetic Basis and Inheritance
Cartilage hair hypoplasia arises from mutations in the RMRP gene. This gene provides instructions for creating a noncoding RNA molecule, rather than a protein. This RNA component is essential for forming an enzyme complex called mitochondrial RNA-processing endoribonuclease, or RNase MRP. The RNase MRP enzyme plays important roles in cellular processes, including the replication of mitochondrial DNA and the processing of ribosomal RNA, which is necessary for building proteins.
CHH is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the mutated RMRP gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene typically do not show symptoms themselves and are known as carriers. If two carrier parents have a child, there is a 25% chance with each pregnancy that their child will inherit two mutated copies and develop CHH.
Key Characteristics and Associated Health Issues
Individuals with cartilage hair hypoplasia exhibit a range of physical characteristics and can experience various health issues. A prominent feature is disproportionate short stature, with notably short limbs. Skeletal findings can include bowed legs, spinal curvature like scoliosis, and changes in the metaphysis of long bones, particularly around the knees. While some joints may have increased flexibility, individuals often have difficulty fully extending their elbows.
The hair in CHH is typically fine, sparse, and lighter in color, a condition known as hypotrichosis. This characteristic appearance is due to a missing core within each hair strand, making the hair thinner. Beyond physical appearance, a significant concern in CHH is varying degrees of immunodeficiency, which can increase susceptibility to infections. Cell-mediated immunodeficiency is commonly reported, leading to potential severe infections.
Individuals with CHH also face an increased risk of blood disorders, such as anemia, which may be more prevalent in childhood but often lessens with age. There is also a higher incidence of certain cancers, including lymphomas, leukemias, and squamous cell carcinoma, particularly in adulthood. Gastrointestinal issues, such as malabsorption and Hirschsprung’s disease, can also occur.
Diagnosis and Identification
Diagnosing cartilage hair hypoplasia involves a combination of clinical evaluation, imaging, and genetic testing. X-rays are an important diagnostic tool, revealing specific skeletal abnormalities such as widened metaphyses, short long bones, and changes in the spine. These radiographic findings provide significant insight, though some features may not become apparent until 9 to 12 months of age.
Genetic testing confirms the diagnosis by identifying mutations in the RMRP gene. Molecular confirmation is important, especially since the RMRP gene is non-coding, meaning some mutations might be missed by certain sequencing methods. For families with a known history of CHH, prenatal diagnosis is possible through genetic testing of fetal DNA, which can identify RMRP mutations before birth. Ultrasound may also show features like limb shortening in the fetus.
Management and Long-Term Care
Managing cartilage hair hypoplasia focuses on addressing specific symptoms and potential complications. Regular medical monitoring encompasses immune function, blood counts, and skeletal health. Given the immune system involvement, prophylactic antibiotics or immunoglobulin replacement therapy may be considered to prevent infections.
Orthopedic interventions, including physical therapy, manage joint mobility and address skeletal issues. Surgical procedures may be necessary for conditions like severe scoliosis, hip dislocations, or lower-extremity misalignments.
For severe anemia, blood transfusions may be required, and in cases of severe immunodeficiency, hematopoietic stem cell transplantation may improve immune function. Individuals with CHH benefit from care provided by a multidisciplinary team of specialists, including orthopedists, immunologists, hematologists, and geneticists.