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Metaphyseal chondrodysplasia, McKusick type(CHH)

MedGen UID:
67398
Concept ID:
C0220748
Congenital Abnormality; Disease or Syndrome
Synonyms: Cartilage hair hypoplasia like syndrome; Cartilage-Hair Hypoplasia; CHH
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:curators]
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Cartilage hair syndrome (7720002); Metaphyseal chondrodysplasia, McKusick type (7720002); Cartilage-hair hypoplasia syndrome (7720002)
 
Gene (location): RMRP (9p13.3)
OMIM®: 250250
Orphanet: ORPHA175

Disease characteristics

The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes the following phenotypes: Metaphyseal dysplasia without hypotrichosis (MDWH). Cartilage-hair hypoplasia (CHH). Anauxetic dysplasia (AD). CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis. The most severe phenotype, AD, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family. [from GeneReviews]
Authors:
Outi Mäkitie  |  Svetlana Vakkilainen   view full author information

Additional descriptions

From OMIM
Cartilage-hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by short-limbed short stature and fine, sparse hair. Additional features include ligamentous laxity, defective immunity, hypoplastic anemia, and neuronal dysplasia of the intestine (summary by Ridanpaa et al., 2001). CHH was first recognized by McKusick et al. (1965) in the Old Order Amish, a religious isolate (see also McKusick, 1978), and was later recognized as exceptionally prevalent in the Finnish population (Makitie, 1992).  http://www.omim.org/entry/250250
From GHR
Cartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis); and abnormal immune system function (immune deficiency) that can lead to recurrent infections.People with cartilage-hair hypoplasia have unusually short limbs and short stature from birth. They typically have malformations in the cartilage near the ends of the long bones in the arms and legs (metaphyseal chondrodysplasia), which then affects development of the bone itself. Most people with cartilage-hair hypoplasia are unusually flexible in some joints, but they may have difficulty extending their elbows fully.Affected individuals have hair that is lighter in color than that of other family members because the core of each hair, which contains some of the pigment that contributes the hair's color, is missing. The missing core also makes each strand of hair thinner, causing the hair to have a sparse appearance overall. Unusually light-colored skin (hypopigmentation), malformed nails, and dental abnormalities may also be seen in this disorder.The extent of the immune deficiency in cartilage-hair hypoplasia varies from mild to severe. Affected individuals with the most severe immune problems are considered to have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi and are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. Most people with cartilage-hair hypoplasia, even those who have milder immune deficiency, experience infections of the respiratory system, ears, and sinuses. In particular, the chicken pox virus (varicella) often causes dangerous infections in people with this disorder. Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs, occur in some people with cartilage-hair hypoplasia. Affected individuals are also at an increased risk of developing cancer, particularly certain skin cancers (basal cell carcinomas), cancer of blood-forming cells (leukemia), and cancer of immune system cells (lymphoma).Some people with cartilage-hair hypoplasia experience gastrointestinal problems. These problems may include an inability to properly absorb nutrients or intolerance of a protein called gluten found in wheat and other grains (celiac disease). Affected individuals may have Hirschsprung disease, an intestinal disorder that causes severe constipation, intestinal blockage, and enlargement of the colon. Narrowing of the anus (anal stenosis) or blockage of the esophagus (esophageal atresia) may also occur.  https://ghr.nlm.nih.gov/condition/cartilage-hair-hypoplasia

Clinical features

Macrocytic anemia
MedGen UID:
1920
Concept ID:
C0002886
Disease or Syndrome
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Neoplasm of the skin
MedGen UID:
40101
Concept ID:
C0007114
Neoplastic Process
A tumor (abnormal growth of tissue) of the skin.
Esophageal atresia
MedGen UID:
4545
Concept ID:
C0014850
Congenital Abnormality
A congenital abnormality of the esophagus in which the upper esophagus ends as a blind pouch and does not connect with the lower esophagus; it is often accompanied by a tracheoesophageal fistula. Signs and symptoms in a newborn with this abnormality include excessive salivation, choking, coughing, and the development of cyanosis and respiratory distress when fed.
Lymphoma
MedGen UID:
44223
Concept ID:
C0024299
Neoplastic Process
A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Aganglionic megacolon
MedGen UID:
6285
Concept ID:
C0025160
Pathologic Function
An abnormal dilation of the colon not due to obstruction.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Fair hair
MedGen UID:
116090
Concept ID:
C0239801
Finding
A lesser degree of hair pigmentation than would otherwise be expected.
Pyle metaphyseal dysplasia
MedGen UID:
82704
Concept ID:
C0265294
Disease or Syndrome
Pyle disease is characterized by long bones with wide and expanded trabecular metaphyses, thin cortical bone, and bone fragility. Fractures are common in Pyle disease, and fracture lines usually go through the abnormally wide metaphyses, revealing their fragility (summary by Kiper et al., 2016).
Fine hair
MedGen UID:
98401
Concept ID:
C0423867
Finding
Hair that is fine or thin to the touch.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
A decrease in the number of neutrophils in the peripheral blood.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Diamond-Blackfan anemia
MedGen UID:
266045
Concept ID:
C1260899
Disease or Syndrome
Diamond-Blackfan anemia (DBA) in its classic form is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in up to 50% of affected individuals, and growth retardation in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life. The phenotypic spectrum ranges from a mild form (e.g., mild anemia, no anemia with only subtle erythroid abnormalities, physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma.
Sparse and thin eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.
Narrow vertebral interpedicular distance
MedGen UID:
318662
Concept ID:
C1832598
Finding
A reduction of the distance between vertebral pedicles, which are the two short, thick processes, which project backward, one on either side, from the upper part of the vertebral body, at the junction of its posterior and lateral surfaces.
Metaphyseal cupping
MedGen UID:
323062
Concept ID:
C1837082
Finding
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Short palm
MedGen UID:
334684
Concept ID:
C1843108
Finding
Short palm.
Sparse eyelashes
MedGen UID:
375151
Concept ID:
C1843300
Finding
Decreased density/number of eyelashes.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The ability of a joint to move beyond its normal range of motion.
Hypoplasia of the odontoid process
MedGen UID:
339524
Concept ID:
C1846439
Finding
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
Neonatal short-limb short stature
MedGen UID:
337984
Concept ID:
C1850171
Finding
A type of short-limbed dwarfism that is manifest beginning in the neonatal period.
Flaring of lower rib cage
MedGen UID:
381581
Concept ID:
C1855196
Finding
Cellular immunodeficiency
MedGen UID:
344444
Concept ID:
C1855204
Finding
An immunodeficiency characterized by defective cell-mediated immunity or humoral immunity.
Susceptibility to chickenpox
MedGen UID:
381583
Concept ID:
C1855205
Finding
Increased susceptibility to chicken pox, as manifested by recurrent episodes of chicken pox.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Sparse facial hair
MedGen UID:
488981
Concept ID:
C2017869
Finding
Reduced number or density of facial hair.
Malabsorption
MedGen UID:
811453
Concept ID:
C3714745
Finding
Impaired ability to absorb one or more nutrients from the intestine.
Abnormality of pelvic girdle bone morphology
MedGen UID:
866545
Concept ID:
C4020847
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Impaired lymphocyte transformation with phytohemagglutinin
MedGen UID:
871152
Concept ID:
C4025625
Finding
Normal peripheral blood lymphocytes, when stimulated by phytohemagglutinin (PHA) are cytotoxic for homologous and heterologous cells but not for autologous cells in monolayer culture. The cytotoxic effect is thought to be indicative of the immunological competence of the lymphocytes.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Metaphyseal chondrodysplasia, McKusick type in Orphanet.

Recent clinical studies

Diagnosis

Sensenbrenner JA
Birth Defects Orig Artic Ser 1974;10(12):422-4. PMID: 4549299

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