Cartilage hair hypoplasia is a rare multisystemic genetic disorder demarcated by a short stature from birth, hypoplastic hair, various skeletal abnormalities and a variable degree of immunodeficiency that can be fatal in the absence of an early diagnosis. Clinical signs, results from imaging studies, and genetic testing are necessary parts of the diagnostic workup.
Signs and symptoms of cartilage hair hypoplasia (CHH) may be evident from birth, when disproportionately short limbs, considered as a cardinal feature of CHH, are identified  . Consequently, a short stature is evident in all patients, with metaphyseal dysplasia being the principal pathological event  . Bowing of the lower extremities, a prominent reduction in the length of the tibia compared to the fibula, very short hands characterized by increased laxity of the metacarpal, interphalangeal and phalangeal joints, and incomplete extension of the elbow joint are important additional skeletal manifestations of CHH  . Apart from growth abnormalities, the appearance of a fine, light-colored and sparse, short hair is the second main component of the clinical presentation . Hypopigmentation of the skin and nail dysplasia can be identified in some cases . Immunodysfunction, humoral and/or cell-mediated, is readily observed, ranging from mild subclinical forms to severe combined immunodeficiency (SCID)  . In fact, neutropenia and lymphopenia frequently create favorable conditions for recurrent infections, seen in up to 60% of patients, and are the principal causes of death in CHH . Gastrointestinal conditions, such as malabsorption, celiac disease or Hirschsprung's disease are identified in about 18% of cases, which may be one of the contributing factors for failure of infants to thrive throughout childhood, another possible symptom . Finally, immunodeficiency combined with anemia that is commonly noted shows a significant predilection toward hematologic malignancies, especially lymphomas  .
CHH must be considered in the differential diagnosis of a short stature that appears from birth and accompanying features such as hair hypoplasia and immunodeficiency that predisposes individuals to recurrent infections. For this reason, a meticulously performed physical examination is a pivotal step. Despite the genetic nature of the disorder, its mode of inheritance (autosomal recessive) does not mandate a positive family history, but nevertheless, the appearance of similar signs and symptoms in close relatives or siblings must be noted. Laboratory studies will reveal transient macrocytic anemia, lymphopenia with a decreased CD4+/CD8+ T-cell count, and neutropenia  . Imaging studies are used to distinguish CHH from numerous other causes of short stature. Metaphyseal dysplasia seen on X-rays of the limbs is the principal radiologic feature, accompanied by thickening and shortening of the tubular bones (distal femur, proximal tibia and bones of the hands), excessive length of the distal fibula, flaring of the costochondral junction, delayed ossification, and cone-shaped phalangeal epiphyses  . If these features are identified during infancy, CHH is a highly likely diagnosis, in which case genetic studies should be pursued to confirm the underlying cause. Sequencing of the mitochondrial RNA-processing (RMRP) gene, the main culprit in the pathogenesis of CHH, located on chromosome 9p13.3  , is available and advised whenever valid clinical suspicion exists based on clinical and radiographic criteria.