What are the other Names for this Condition? (Also known as/Synonyms)

• Cartilage-Hair Hypoplasia-like Syndrome
• CHH (Cartilage-Hair Hypoplasia)
• Metaphyseal Chondrodysplasia, McKusick type

What is Cartilage-Hair Hypoplasia? (Definition/Background Information)

• Cartilage-Hair Hypoplasia (CHH) 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
• Signs and symptoms may vary among affected individuals. People with this condition are also at an increased risk of developing cancer, particularly blood, skin, and immune system cancers. Gastrointestinal problems are also common
• Cartilage-Hair Hypoplasia is caused by mutations in the RMRP gene and is inherited in an autosomal recessive fashion

(Source: Cartilage-Hair Hypoplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Cartilage-Hair Hypoplasia? (Age and Sex Distribution)

• Cartilage-Hair Hypoplasia is a rare, congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• The condition is most frequent in the Old Order Amish (occurring at a frequency of approximately 1:1,300) and Finnish populations (occurring at a frequency of approximately 1:20,000)

What are the Risk Factors for Cartilage-Hair Hypoplasia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Cartilage-Hair Hypoplasia is an inherited condition
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cartilage-Hair Hypoplasia? (Etiology)

• Cartilage-Hair Hypoplasia is caused by mutations in the RMRP gene and is inherited in an autosomal recessive fashion

(Source: Cartilage-Hair Hypoplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Cartilage-Hair Hypoplasia?

The signs and symptoms of Cartilage-Hair Hypoplasia may vary from one individual to another and may be mild or severe. Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Abnormal vertebral ossification
• Abnormality of epiphysis morphology
• Abnormality of retinal pigmentation
• Abnormality of the cardiac septa 
• Abnormality of the distal phalanx of finger
• Abnormality of the pancreas 
• Biconvex vertebral bodies 
• Blue sclerae 
• Cardiomyopathy 
• Convex nasal ridge
• Diaphyseal thickening
• EEG abnormality 
• Failure to thrive
• High-grade hypermetropia
• Hyperlordosis
• Hypocalcemia
• Large face
• Limited elbow extension
• Mesomelia 
• Metaphyseal chondrodysplasia 
• Micromelia 
• Muscular hypotonia 
• Neutropenia
• Respiratory insufficiency
• Rhizomelia 
• Scoliosis 
• Short neck
• Short palm
• Sparse and thin eyebrow
• Sparse hair 
• Spinal dysraphism 
• Strabismus
• Tibial bowing
• Tracheal stenosis
• Visual impairment

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the hip bone
• Abnormality of the palate
• Depressed nasal bridge
• Flaring of lower rib cage 
• Gingival overgrowth
• Low-set, posteriorly rotated ears 
• Malabsorption
• Mucopolysacchariduria 
• Myopia
• Narrow chest
• Prominent forehead
• Reduced tendon reflexes

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of chromosome stability 
• Accelerated skeletal maturation 
• Aganglionic megacolon 
• Anemia 
• Anteverted nares
• Aplasia/hypoplasia affecting the eye
• Aplasia/hypoplasia of the abdominal wall musculature
• Brachycephaly 
• Cognitive impairment
• Decreased antibody level in blood 
• Delayed skeletal maturation
• Depressed nasal ridge
• Epicanthus
• Heart block 
• Hepatomegaly
• Hypoplasia of the odontoid process 
• Joint hyperflexibility 
• Lymphoma 
• Macrotia
• Pectus carinatum
• Sacral dimple
• Short thorax 
• Small hand
• Wide nasal bridge

Some additional signs and symptoms:

• Abnormality of pelvic girdle bone morphology
• Cellular immunodeficiency 
• Congenital hypoplastic anemia 
• Esophageal atresia 
• Fair hair
• Femoral bowing
• Fine hair
• Impaired lymphocyte transformation with phytohemagglutinin 
• Joint hypermobility
• Lumbar hyperlordosis 
• Lymphopenia
• Macrocytic anemia 
• Metaphyseal cupping 
• Metaphyseal dysplasia 
• Metaphyseal widening
• Narrow vertebral interpedicular distance
• Neonatal short-limb short stature
• Neoplasm of the skin
• Sparse eyelashes
• Sparse facial hair 
• Susceptibility to chickenpox

(Source: Cartilage-Hair Hypoplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Cartilage-Hair Hypoplasia Diagnosed?

Cartilage-Hair Hypoplasia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cartilage-Hair Hypoplasia?

The complications of Cartilage-Hair Hypoplasia may include:

• Low self-esteem due to short stature and abnormalities in appearance
• Intestinal blockage
• Severe constipation
• Severe combined immunodeficiency (SCID)
• Damage to tissue and organs due to recurrent infections
• Risk of development of some types of cancer (such as basal cell carcinoma)

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Cartilage-Hair Hypoplasia Treated?

There is no cure for Cartilage-Hair Hypoplasia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Cartilage-Hair Hypoplasia be Prevented?

Cartilage-Hair Hypoplasia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Cartilage-Hair Hypoplasia? (Outcomes/Resolutions)

• The prognosis of Cartilage-Hair Hypoplasia is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Cartilage-Hair Hypoplasia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/