Cartilage Hair Hypoplasia

Cartilage Hair Hypoplasia (CHH) is also known as metaphyseal dysplasia, McKusick type. The disorder was recognized as a clinical entity in 1965, when Victor McKusick and colleagues described the condition in an inbred Amish population (1). The term “metaphyseal” relates to the metaphysis, which is the wide region located at the ends of long bones. The name “Cartilage Hair Hypoplasia” was coined due to the characteristic features: fine, sparse hair and cartilage abnormalities.

 
How Cartilage Hair Hypoplasia Is Inherited

Cartilage Hair Hypoplasia is typically inherited in an autosomal recessive manner (2).

 
Causes of Cartilage Hair Hypoplasia

This dysplasia is caused by a mutation of the gene encoding the RNA component of the ribonuclease mitochondrial RNA processing complex (RMRP). The locus of the RMRP gene is on chromosome 9p13. The mutation affects cartilage development.

 
Physical Characteristics

Cartilage Hair Hypoplasia is a relatively rare congenital disorder. It is most prevalent among the Old-world Amish and Finnish populations. Among Amish people, the incidence is approximately 1.5 in 1000 live births, whereas in Finland, it is 1 in 18,000 to 23,000 (2).

The physical characteristics of Cartilage Hair Hypoplasia include a short limbed form of disproportionate short stature with fine, sparse hair. Intelligence is typically average.

Face and Skull:
  • Relatively average face and skull
  • Fine, sparse, and light hair
  • Sparse eyebrows and eyelashes
Trunk, Chest and Spine:
  • Anterolateral chest deformity
  • Prominent sternum
  • Moderately flared lower rib cage
Arms & Legs:
  • Rhizomelic shortening of the limbs
  • Limited elbow extension, but otherwise ligamentous laxity
  • Short and pudgy hands and feet
  • Possible ankle deformity due to the excessive distal length of
    the fibula
  • Mild bowing of the legs
  • Flat feet
  • Prominent heels
What are the X-ray characteristics?

The major radiographic features in infancy include shortened long tubular bones. The femur is curved with rounded distal epiphyses. Anterior angulation of the sternum and short ribs are also characteristic. The radiographic features in children and adults include short, flared, and irregularly sclerotic metaphyses of tubular bones.

Deformities are more prominent in the knee region than in the proximal femur. A postero-lateral subluxation of the radial head is observed in some patients. The fibula is disproportionately long, most notably at the distal end.

There is minimal craniocaudal widening of interpediculate distance in lumbar spine. Small sagittal and coronal diameters of the vertebrae are typical. Flaring and cupping at the costochondral junction of ribs is also characteristic. The metacarpals and phalanges are severely affected.

 
Making the Diagnosis

In infancy, diagnosis of Cartilage Hair Hypoplasia is difficult; not until 9 to 12 months of age do the abnormalities become apparent. Radiographic examination provides the greatest insight. Widened metaphyses, short long bones, elongated fibulae, and anterior angulation of the sternum are all indicative of Cartilage Hair Hypoplasia. Hair hypoplasia is only a positive criterion; the absence of hair hypoplasia does not warrant the exclusion of Cartilage Hair Hypoplasia as a possible diagnosis.

 
Musculoskeletal Problems
Bowing of Legs

Mild bowing of the legs, either genu valgus or genu varum is characteristic and may require corrective osteotomy. Subluxation of the hips may require also surgery. Legg-Perthes disease has been reported in both male and female patients.

Scoliosis

Scoliosis is typical of Cartilage Hair Hypoplasia. Depending on the degree of curvature, it can be managed observation, bracing, or surgery.

 
Problems Elsewhere in the Body
Intestinal Malabsorption

Intestinal malabsorption occurs in approximately 10% of patients. The intestinal malabsorption problem tends to improve on its own.

Hirschsprung Disease

Hirschsprung Disease occurs in approximately 10% of patients. Surgical intervention is oftentimes necessary. Postoperative mortality rates are nearly 40%, due to severe enterocolitis-related septicemia and a compromised immune system.

Humoral Immunity

Humoral immunity is typically compromised. Nearly 56% of younger children experience recurrent infections, especially respiratory tract infections. Children are unusually susceptible to chicken pox. In McKusick’s original study, 6 patients died due to fatal varicella pneumonia. Currently, Acyclovir is most often prescribed to treat the varicella. Patients have a predisposition to cancer, especially non-Hodgkin’s lymphoma and basal cell carcinoma. Again, this susceptibility is due to the compromised T-cell immunity.

Anemia

Anemia can occur in varying degrees in childhood. In anemic patients, decreased red blood cell proliferation is also observed. Most anemic patients recover spontaneously by adulthood; however fatal hypoplastic anemia can occur in infants. The prevalence of anaemia seems to correlate to the severity of the immunodeficiency and the degree of growth failure.

 
What to Look For

It is vital to keep a close watch for the possibility of serious infection or malignancy. Varicella and other live virus vaccinations should not be given if the diagnosis is established.

 
References
  1. McKusick, V. A.; Eldridge, R.; Hostetler, J. A.; Egeland, J. A.; Ruangwit, U. Dwarfism in the Amish. II. Cartilage-hair hypoplasia. Bull. Johns Hopkins Hosp. 116: 285-326, 1965.
  2. Mäkitie, Outi. Cartilage-Hair Hypoplasia: Clinic radiological and genetic study of an inherited skeletal dysplasia. University of Helsinki, Finland. 1992.

Trusted Insights from Nemours' KidsHealth