Boy, 7 months of age, with healthy nonconsanguineous Spanish parents. He was born at 40 weeks, with a weight of 3200g, length of 45cm and head circumference of 36cm. He was admitted at 4 months of age with acute gastroenteritis. The physical examination revealed sparse, fine and brittle hair, shortened limbs, moderate varus bowing of the femurs, and short fingers. His height was 65.5cm (−1.31SD) and his weight 7850g (−0.72SD). Bone radiography showed shortening of long bones and metaphyseal widening. Immunologic testing showed moderate neutropaenia and lymphocytopaenia (reduced T CD4+ and B+T cells); low levels of IgA and normal IgM and IgG levels. These findings led to a clinical diagnosis of cartilage-hair hypoplasia. An RMRP test was ordered at 3 years of age, which detected the presence of 2 heterozygous mutations [g.236A>G, paternal; g.260G>A, maternal]. This diagnosis allowed for screening the maternal blood for the paternal mutation in the foetal DNA (noninvasive prenatal technique) at 8 and 10 weeks in the 2 subsequent gestations of this couple. In the first of these pregnancies, the paternal mutation in the foetal DNA was detected in maternal blood and confirmed by amniocentesis (invasive technique). The pregnancy was terminated. The paternal mutation was not detected in the second pregnancy, and this finding was confirmed by an invasive prenatal test (healthy noncarrier foetus, publication in progress). At 9 years of age, the patient still has short stature (height 108cm [−4.06SD]; weight 20kg [−2.25SD]), and moderate varus bowing of the limbs with followup in the rehabilitation department. His hair is sparse. The patient has had 2 episodes of pneumonia in which no pathogen was identified. His vaccinations are up to date with the immunisation schedule of his autonomous community, and the patient had mild febrile reactions to live virus vaccines. The patient is receiving prophylaxis with trimethoprim-sulfamethoxazole 3 days a week (Fig. 1).

Figure 1.

Top: case 1 patient at 9 and 18 months, and at 5 and 7 years, respectively. Mutations found in the RMRP gene. Bottom: case 2 patient at 4.5 years of age and radiographs at 2 years of age.

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Boy aged 2.3 years of Romanian descent diagnosed with achondroplasia at one week of life. The parents were nonconsanguineous, the pregnancy was monitored in Romania, and the patient was born to term; the birth anthropometric measurements are not known. Physical examination showed a height of 62cm (−9.6SD), weight of 8620g (−3.34SD), shortening of upper and lower extremities, thick hands and short fingers. There were no skull abnormalities, and the hair was sparse, very fine and blonde. Bone radiography showed short hand bones with cone-shaped epiphyses, knees with broad and irregular metaphyses and poorly ossified epiphyses, femoral bowing with delayed ossification of the proximal femoral epiphyses, and hip bones with normal acetabula (Fig. 1). Laboratory tests were performed (complete blood count, biochemistry panel, and immunoglobulins) the results of which were normal. At 7.4 years of age he was 90.6cm tall (−6.2SD), had a growth rate of 4–7cm a year (−2.1SD and −1.4SD), he had not developed any severe infections or any type of gastrointestinal malabsorption. We ordered a direct RMRP gene test that revealed 2 heterozygous mutations (g.96_97dupTG, maternal; g.-25-11 dupACTACTCTGTGAAGC). The father did not cooperate (Fig. 1).

The mutations found in these 2 cases have been described previously in patients of European descent with a cartilage-hair hypoplasia phenotype.4 The g.-25-11 dupACTACTCTGTGAAGC mutation in the Romanian patient has been described in a patient of Spanish descent.5Table 1 shows the differential diagnosis. A full diagnosis based on clinical and molecular findings can help predict the prognosis of the disease and inform its management. Immune function, both humoral (IgG deficiency) and cellular (lymphocytopaenia), and the presence of nonregenerative macrocytic anaemia should be evaluated. These patients may also develop malignancies, especially of the blood (lymphomas and leukaemia).6 Possible treatments include osteostomies to correct deformities, surgical bone lengthening, infection prophylaxis in the presence of an immunodeficiency, and prophylactic treatment for anaemia, should it develop. Molecular diagnosis makes it possible to provide adequate genetic counselling for family planning and reproductive health.