cartilage hair hypoplasia ( chh ) , also named mckusick type metaphyseal chondrodysplasia , is a rare hereditary disorder with autosomal recessive mode of inheritance ( online mendelian inheritance in man : omim250250 ) 
 ( 1 - 3 ) . the hallmark of the disease is a combination of the metaphyseal chondrodysplasia and characteristic hair , which is also diagnostic for chh . the mutation in the rmrp gene ( 9p12 ) is responsible for the disease 
 ( 1,2,6,7 ) . the patients with cartilage hair - hypoplasia are symptomatic at birth including short puffy hands and multiple skin folds around the neck and extremities . although the size of head is normal , the scalp hairs , the eyebrows , and the eyelashes are blond , fine , and scattered . other symptoms and signs may present later during life . short stature with a final adult height of 107 - 157 cm ( 40 - 60 in ) apart from short - limbed short stature and  abnormal hair , immunodeficiency is another characteristic feature of this disease . the immune deficiency in chh may be an isolated b - cell or t - cell immunodeficiency , or combined b - cell and t - cell immunodeficiency 
 ( 9 - 11 ) . gastrointestinal disorders ( such as hirschsprung disease , primary mal - absorption , anal stenosis and esophageal atresia ) occur in approximately 18% of the patients while hirschsprung disease is the most common one among them ( 9%)(712 ) ( 7 , 12 ) . an eight - year - old boy was visited in endocrinology clinic of the kashan university of medical sciences . he was 15.5 kg in weight ( 3.5 standard deviation below mean ) and his height was 92 cm ( 7 standard deviation below mean ) . based on the available documents , he weighed 3.65 kg ( 50th centile ) at birth , with a crown to heel length of 47 cm ( 10th centile ) . he had shown abdominal distention and vomiting in his neonatal period and eventually diagnosed ashirschsprung disease that was confirmed using biopsy . 
 
 in physical examination he had severe short stature , disproportionate short - limbed dwarfism , short and puffy hands , and genu varum deformity . his scalp hairs , eyebrows , and eyelashes were fair , very fine and sparse ( fig . while no nail dysplasia or dental abnormality was found , intellectual development was normal for his age and no clinical evidence of immunodeficiency was observed . a 3-mm kidney stone was detected when he was 3 years old that enlarged to 8 mm in size at the age of 8 and treated by lithotripsy . hair of the scalp , eyebrows , and eyelashes is light , fine , and sparse . skeletal x - rays revealed typical metaphyseal dysostosis , including widening , cupping , and defective mineralization in the metaphysis of the tubular bones ( fig . sterile pyuria was found in several samples of urinalysis that may be as a result of the vesicouretral reflux or renal stone . the patient had been assessed for celiac disease and cystic fibrosis during his infancy that was negative . x - rays of his right and left lower limbs show metaphyseal changes ( cupping , widening , fraying and sclerosis of the femur and tibia ) . based on our literature review , this is the first report of cartilage hair hypoplasia in iran . cartilage hair hypoplasia originally described by mckusik et al in 1964 in amish children , and later has been described in non - amish persons throughout the united states , europe , and mexico . the genetic defect in cartilage hair hypoplasia is mutations in the rmrp gene , mapped to 9p12(7 ) . rnase rmrp has 2 functions : cleavage of rna in mitochondrial dna synthesis and nucleolar cleaving of preribosomal rna ( pre - rrna ) . was reported to be 1 per 1340 population with a carrier rate of 1 per 19 population ( 3).in finland ,  the frequency of cartilage hair hypoplasia was reported to be  1 case per 23000 live births , with a carrier rate of 1 case per 76 live births . cartilage hair hypoplasia has a diverse distribution of signs and symptoms including short stature ( 100% ) , skeletal dysplasia ( 100% ) , hair hypoplasia ( 93% ) , hypoplastic anemia of childhood ( 79% ) , immunodeficiency ( 56% ) , skin hypopigmentation , nails dysplasia , failure to thrive , gastrointestinal diseases ( 18% ; including hirschsprungs , malabsorption , celiac disease ) , defective spermatogenesis , and increased risk of malignancies ( 13 ) . later he was referred to our clinic at the age of eight due to severe short stature . radiographic features of cartilage hair hypoplasia are short and thick long bones with irregular metaphyseal borders of the growth plates , excessive distal length of the fibula , flaring and irregularity of the ribs at the costochondral junction ( 4 ) . the metaphyseal ends are widened , scalloped and irregularly sclerotic , often with cystic areas ; the epiphyses are less affected . the radiologic changes are most prominent in the knees and ankles ; the hips are only mildly affected . delayed ossification of the long bones are also characteristic findings on x - rays(4,14 ) . the costochondral junctions may show rachitic like changes ( like harrison grooves ) and anterolateral chest deformity may be seen . these radiographic features develop by age 6 - 9 months and are diagnostic . during adulthood with the closure of the epiphyseal plates , hand and wrist x - rays may show rachitic changes and may be relatively normal . analyzed 149 skeletal radiographic surveys of 82 finnish chh patients ; skeletal age delay was observed in 14% of patients . the vertebral bodies are usually normal and caudal widening of the interpediculate distances ( though less obvious than normal ) is present in most patients . they reported angulation of the entire sternum , a sign not previously described in chh ( in a 2-week - old girl who also showed short ribs with anterior flaring ) . they also reported a 5-month - old girl with widening of the atlanto - axial space on lateral cervical spine radiograph ( 14).bonafe et alsuggested that a diagnostic sign of chh is cone - shaped epiphyses in the phalanges . patients with metaphyseal chondrodysplasia and cone - shaped epiphyses , should be evaluated for the presence of rmrp mutations even if they have not the other evidences of disease(15 ) . sequence analysis of rmrp identifies two causative mutations in the great majority of probands with a presumed diagnosis of a chh - ad spectrum disorder , thus confirming the clinical diagnosis . our patient had disproportionate short - limbed dwarfism , short and puffy hands and genu varum deformity . interestingly , his left hand x - ray was normal but he had typical metaphyseal changes of rickets in the lower extremities ( cupping , widening , fraying and sclerotic changes in the metaphysis of both femur and tibia , fig.2 ) . he had developed a 3 mm kidney stone when he was 3 years old that reach to 8 mm size at the age of 8 that treated by lithotripsy . because of the high rate of consanguineous marriages in iran and an increased rate of autosomal recessive disorders , we recommend physicians to consider chh in the differential diagnosis of severe short stature associated with metaphyseal chondro - dysplasia , hair hypoplasia and skin hypopigmentation . it should be noted that in cases without evidence of metaphyseal abnormality in hand x - rays , it might be found in lower extremities . moreover , these patients may be at an increased risk for vesicouretral reflux , renal stone , or hypothyroidism .
cartilage hair hypoplasia ( chh ) , is a rare cause of metaphyseal chondrodysplasia and short stature . other featuresincluded hair abnormality , immunodeficiency , anemia , gastrointestinal disorders ( hirschsprung disease , celiac ,  ) and increased risk of cancer . 
 the disease is an autosomal recessive disorder and previously has notbeen reported in iran . 
 we report a 9-year - old boy diagnosed as cartilage hair hypoplasia , with severe short stature , metaphyseal chondrodysplasia , hair hypoplasia , hirschsprung disease , hypothyroidism , vesicouretral refluxand renal stone . 
 renal stone and hypothyroidism have been reported in cartilage hair hypoplasia with lower frequencies.this is the first report of cartilage hair hypoplasia in iran .