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 [1] [2]. Consequently, a short stature is evident in all patients, with metaphyseal dysplasia being the principal pathological event [2] [3]. 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 [2] [3]. Apart from growth abnormalities, the appearance of a fine, light-colored and sparse, short hair is the second main component of the clinical presentation [2]. Hypopigmentation of the skin and nail dysplasia can be identified in some cases [4]. Immunodysfunction, humoral and/or cell-mediated, is readily observed, ranging from mild subclinical forms to severe combined immunodeficiency (SCID) [2] [3]. 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 [3]. 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 [4]. Finally, immunodeficiency combined with anemia that is commonly noted shows a significant predilection toward hematologic malignancies, especially lymphomas [2] [3].

• Short Stature

  We conclude that recessive metaphyseal dysplasia without hypotrichosis is a variant of CHH, manifesting only as short stature and metaphyseal dysplasia. [ncbi.nlm.nih.gov]

• Anemia

  Anemia is seen in over 80% of patients with cartilage-hair hypoplasia (CHH). While this is usually mild and self-limited, some patients demonstrate a severe, persistent anemia resembling that seen in Diamond-Blackfan anemia (DBA). [ncbi.nlm.nih.gov]

  We did not observe an anemia phenotype. [dukespace.lib.duke.edu]

  There is considerable variability in these characteristics as well as others such as susceptibility to infections, anemia, skin color, and bowel problems. [wohproject.org]

• Hodgkin Lymphoma

  CONCLUSIONS: This study confirms an increased risk of cancer, especially non-Hodgkin's lymphoma, probably attributable to defective immunity, among patients with CHH. [ncbi.nlm.nih.gov]

  There were no national reference rates available for non-Hodgkin's lymphomas alone, but based on experience of the Finnish Cancer Registry, lymphomas comprise about two thirds of the deaths among the haematological cancers. [adc.bmj.com]

  The most common cancers are non-Hodgkin lymphoma, squamous cell carcinoma, leukemia, and Hodgkin lymphoma. The reason why individuals with McKusick type metaphyseal chondrodysplasia have increased risks for cancer is unclear at this time. [rarediseases.org]

• Recurrent Infection

  It is characterized by disproportionate short stature, fine sparse hair, ligamentous laxity, hematological abnormalities with anemia, a predisposition to malignant tumors, and recurrent infections usually due to cellular and/or humoral immunodeficiency [ncbi.nlm.nih.gov]

  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. [symptoma.com]

• Weight Gain

   Treatment :  Caution regarding weight gain  Treat limb alignment and perform early joint replacement  Shelf acetabular augmentation in some patients - to improve coverage of the misshapen femoral head  Osteotomies may be helpful in realigning [slideshare.net]

• Failure to Thrive

  We report on a Thai girl who first presented with chronic diarrhea, recurrent pneumonia, and severe failure to thrive, without apparently disproportionate dwarfism. [ncbi.nlm.nih.gov]

  - Gastrointestinal dysfunction: This can present with signs of malabsorption, diarrhea, celiac disease, and failure to thrive. This requires symptomatic treatment. [atlasgeneticsoncology.org]

  Intestinal malabsorption presents as diarrhea, and decreased ability to gain weight (failure to thrive) in the newborn period. Most of the intestinal symptoms appear within the first two years of life. [rarediseases.org]

  OS is usually accompanied by enlarged lymphoid tissues, protracted diarrhea, failure to thrive, and eosinophilia, which refers to the condition characterized by the presence of high amounts of eosinophils in either the blood or body tissues 21. [doi.org]

• Lordosis

  Increased ligamentous laxity was present in 95%, limited extension of the elbows in 92%, increased lumbar lordosis in 85%, thoracal deformity in 68%, genu varum in 63% and scoliosis in 21% of the patients. [ncbi.nlm.nih.gov]

  […] peptide (PTHRP) receptor mental retardation short limbed dwarfism wide eyes monkey like stance ostebulbous metaphyseal expansion of long bones seen on xray Schmid's autosomal dominant defect in Type X collagen short limbed dwarfism excessive lumbar lordosis [orthobullets.com]

   Lumbar stenosis & excessive lordosis with spinal cord / nerve root compression  Radial head subluxation  Normal intelligence but delayed motor milestones 10. [slideshare.net]

• Short Hands

  Other symptoms include short hands and possibly short, deformed limbs (varus). X-ray reveals metaphyseal lesions, especially in the knees, and large, round epiphyses during childhood. [orpha.net]

  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 [symptoma.com]

• Short Arm

  We have previously mapped the gene for CHH to the short arm of chromosome 9 in Finnish and Amish families. The CHH locus resides close to D9S163 within an interval of 1.5 cM flanked by D9S165 and D9S50. [ncbi.nlm.nih.gov]

  The locus of the gene has been mapped to the short arm of chromosome 9. Patients with CHH usually suffer from cellular immunodeficiency. [en.wikipedia.org]

  arms and legs (short-limbed dwarfism), increased joint mobility (hypermobility), and fine silky hair. [rarediseases.org]

  Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia. Genomics 14, 437–443 (1992). 21 Anderson, M.A. & Gusella, J.F. [doi.org]

  And a little girl who would grow up to be four feet tall with exceedingly short arms and legs does not fit that paradigm. Seventeen years later, we are on the verge of being able to do something when our image of perfection is threatened. [theguardian.com]

• Short Extremities

  Before birth Possibly via prenatal ultrasound due to short extremities Genetic sampling if expected After birth X-ray findings Observation of common physical characteristics Confirmation by DNA testing of the RMRP gene via a blood test What are the common [littlepeopleuk.org]

  short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. [ncbi.nlm.nih.gov]

• Platyspondyly

  […] small chest with short ribs Plain radiograph short, bowed femurs with metaphyseal flare and irregularity eleven ribs, moderately short Flared and irregular metaphyses of multiple long bones are also associated with these dysplasias, as well as mild platyspondyly [radiopaedia.org]

   Generalised severe platyspondyly  Increased intervertebral disc height  Open staircase vertebrae  Kyphosis/ scoliosis  Widening sclerosis irregularity of tubular bones  Irregular femoral epiphysis  Retarded bone maturation 17. [slideshare.net]

• Hair Hypoplasia

  Pour citer ce document : URI: http://hdl.handle.net/2042/38617 | DOI : https://doi.org/10.4267/2042/38617 Title: Cartilage-hair hypoplasia (CHH) Author: Hermanns, P ; Lee, B Description: Review on Cartilage-hair hypoplasia (CHH), with data on clinics, [documents.irevues.inist.fr]

  Irwin GAL (1966) Cartilage-hair hypoplasia (CHH) Variant of familial metaphyseal dysostosis. Radiology 86:926–928 PubMed Google Scholar 12. Kaitila I, Perheentupa J (1980) Cartilage-hair hypoplasia. [doi.org]

  CARTILAGE-HAIR HYPOPLASIA. ' Bulletin of the Johns Hopkins Hospital, vol. 116, pp. 285-326. @article{148e73b0ed6a49efb0f877d6636f271e, title = "DWARFISM IN THE AMISH. II. CARTILAGE-HAIR HYPOPLASIA.", author = "MCKUSICK, {V. A.} and R. [miami.pure.elsevier.com]

  Sulisalo T, Van der Burgt I, Rimoin D, et al (1995) Genetic homogeneity of cartilage-hair hypoplasia. Hum Genet 95:157–160 PubMed Google Scholar 14. [springerlink.com]

  Diverse autoantibody reactivity in cartilage-hair hypoplasia. [ncbi.nlm.nih.gov]

• Sparse Hair

  Cartilage-hair hypoplasia (CHH) is a rare autosomal-recessive disorder characterized by short-limbed dwarfism, sparse hair, and immune deficiency. [ncbi.nlm.nih.gov]

  From Wikidata Jump to navigation Jump to search A metaphyseal dysplasia that results_in short-limbed dwarfism and fine sparse hair. [wikidata.org]

• Skin Lesion

  We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. [ncbi.nlm.nih.gov]

  Pre-existing autoimmunity and inflammatory skin lesions were a prominent feature in 5 of 16 patients (patient nos. 3, 5, 8, 11, and 12; Table 1 ). Thirteen patients were transplanted in early childhood (mean age 2.5 years). [bloodjournal.org]

• Alopecia

  This study suggests that Hirschsprung disease is associated especially with severe cartilage-hair hypoplasia: the patients with Hirschsprung disease had severe growth failure and a higher incidence of alopecia, infections, malignancies, and childhood [ncbi.nlm.nih.gov]

  About 15% of affected individuals have complete hair loss (alopecia), which includes the scalp, eyelashes, eyebrows, and body hair. Decreased red blood cell production (anemia) has been reported in about 80% of affected individuals. [rarediseases.org]

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 [2] [3]. 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 [3] [4]. 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 [1] [2], is available and advised whenever valid clinical suspicion exists based on clinical and radiographic criteria.

• Anergy

  A 29-year-old white woman had short limbs, hyperextendable joints, fine skin and body hair, anergy to common skin test antigens, subnormal lymphocyte response to phytohemagglutinin, and increased numbers of natural killer cells, characteristic of cartilage-hair [ncbi.nlm.nih.gov]

• Lymphopenia

  Here, we present a case of CHH with mild skeletal changes and immunological findings associated with recurrent otitis media, neutropenia, and lymphopenia. [ncbi.nlm.nih.gov]

  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. [symptoma.com]

After the surgery, we continued GH treatment. Additional GH treatment of 3.6 more years had kept his height to -2.0 SD. [ncbi.nlm.nih.gov]

Treatment: There is no known treatment for the short stature and sparse hair. Conventional medical and surgical treatment for aganglionosis and malignancies should be used. [wohproject.org]

Prognosis The prognosis depends on the presence and severity of the immune deficiency and the possible association with Hirschsprung disease (see this term). The documents contained in this web site are presented for information purposes only. [orpha.net]

CONCLUSIONS: HD associated with CHH has poor prognosis in terms of postoperative morbidity and risk of death. These patients require particular attention during postoperative follow-up to detect potentially lethal complications. [ncbi.nlm.nih.gov]

The etiology of this finding remains unclear. Some causes of such deposits can be of a reversible nature, thus prompting early recognition although their consequences on clinical outcome remain mostly unknown. [ncbi.nlm.nih.gov]

Etiology Mutations in the RMRP (RNA component of mitochondrial RNA-processing endoribonuclease) gene, which maps to the 9p21-p12 locus, are responsible for the disease. [orpha.net]

An epidemiological and genetic study of CHH in Finland showed 107 patients, 46 males and 61 females, in 85 families. Eighteen of them had died, seven before the age of 1 year. The living patients ranged in age from 1 to 51 years, median 21 years. [ncbi.nlm.nih.gov]

Summary Epidemiology Prevalence is unknown. Clinical description The disease is associated with fine, slow growing hair, and sometimes with immune deficiencies. Other symptoms include short hands and possibly short, deformed limbs (varus). [orpha.net]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]

PURPOSE OF REVIEW: To report on the expanding clinical and immunological spectrum associated with ribonuclease mitochondrial RNA-processing mutations and to review the cellular and molecular mechanisms involved in the pathophysiology of cartilage-hair [ncbi.nlm.nih.gov]

However, the specific role of ribosomal and extraribosomal defects in the pathophysiology of the various phenotypic features of CHH remains undefined. Development of suitable animal models is needed to address this important issue. [scienceopen.com]

Here, we critically review the underlying genetics in old and new ribosomopathies and examine the pathophysiologic consequences of aberrant ribosome biogenesis. [els.net]

Introduction Heterogeneous group of disorders characterized by metaphyseal changes of the tubular bones with normal epiphyses Epidemiology incidence skeletal dysplasias occur at a rate of 2 to 3 newborns per 10,000 births Pathophysiology metaphyseal dysplasia [orthobullets.com]

We strive to maximize children’s mobility, correct deformity, and prevent future complications. [nemours.org]

In this patient, long-term administration of granulocyte colony-stimulating factor increased peripheral neutrophil counts and prevented recurrent hospitalizations for bacterial lower respiratory tract infections. [ncbi.nlm.nih.gov]

He also suggested regular doctor visits with preventative scans, to ensure that she lives for many years to come. [recapo.com]

But when I looked for what Counsyl rather ominously calls "preventable genetic diseases" that are covered by its test, I immediately saw two forms of dwarfism. [theguardian.com]

In addition, the recent demonstration that RMRP forms a complex with TERT provides strong evidence to a role of RMRP in prevention of cellular senescence and maintenance of telomere homeostasis. 6 Reduced thymic output of patients with CHH and combined [bloodjournal.org]

1. Horn J, Schlesier M, Warnatz K, et al. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia. Hum Immunol. 2010;71(9):916-919.
2. Riley P, Weiner DS, Leighley B, et al. Cartilage hair hypoplasia: characteristics and orthopaedic manifestations. J Child Orthop. 2015;9(2):145-152.
3. Baradaran-Heravi A, Thiel C, Rauch A, Zenker M, Boerkoel CF, Kaitila I. Clinical and Genetic Distinction of Schimke Immuno-Osseous Dysplasia and Cartilage-Hair Hypoplasia. American journal of medical genetics Part A. 2008;146A(15):2013-2017.
4. Shiasi Arani K. Cartilage Hair Hypoplasia: First report from Iran. Med J Islam Repub Iran. 2013;27(3):157-160.