Clinical Guidance

The CHH-AD spectrum includes a range of phenotypes. RMRP is not translated into a protein; thus, genotype-phenotype correlation depends on the position of the pathogenic variant in the transcript and the proposed effect on transcript folding and RNA-protein interaction . The milder phenotypes are usually caused by either of the following:

• Compound heterozygous or homozygous pathogenic variants within the transcript resulting in little to intermediate effect on the function of RNase MRP

• Compound heterozygosity for one pathogenic variant within the transcript and one pathogenic variant in the promoter region

AD is caused by either of the following:

Source: GeneReviews — "Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders"

Diagnostic Criteria

There are no formal diagnostic criteria for cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders, as individuals present with highly variable phenotypes. The CHH-AD spectrum disorders are a continuum ranging from short stature without hypotrichosis with only radiographic evidence of metaphyseal dysplasia (MDWH) , to short stature with hypotrichosis and variable metaphyseal dysplasia of the tubular bones (cartilage-hair hypoplasia [CHH]) , to severe deforming short stature with metaphyseal, epiphyseal, and vertebral dysplasia (anauxetic dysplasia [AD]) . Newborn screening for severe combined immunodeficiency (SCID) using detection of T cell receptor excision circles is able to identify some individuals with CHH prior to recognition of other findings .

Source: GeneReviews — "Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders"

Differential Diagnosis

Table 2. Genes of Interest in the Differential Diagnosis of Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders

Management Guidelines

No clinical practice guidelines for cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders have been published. Guidelines for the management of immunodeficiency in CHH have been published .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with a CHH-AD spectrum disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Musculoskeletal

| Full skeletal survey | To incl (in AD) views of cervical spine to identify cervical vertebral abnormalities assess risk of atlantoaxial subluxation

Orthopedic consult | Eval for complications of joint laxity, lumbar lordosis, chest deformity, scoliosis, varus deformity of lower extremities

Allergy/Immunology

| Assess for immunodeficiency:1

• Serum concentration of IgG, IgA, IgM, IgG subclasses

• CD3, 4, 8, 19, 16/56

• Post-vaccine titers

• Other immunologic parameters: allogeneic lymphocyte cytotoxicity; T cell subsets, TREC analysis; T cell repertoire; proliferation response to PHA; proliferation response to anti-CD3

| Immunology consultation in those w/abnormal immunologic testing or recurrent infections for assessment treatment to determine vaccination program approach to varicella prophylaxis

Respiratory

| Pulmonary consult | Eval for evidence of re...

Source: GeneReviews — "Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders"

Clinical Guidance

Immunization with live vaccines should be carefully considered in those with CHH and evidence of abnormal immunologic function and should be avoided in those with CHH and severe combined immunodeficiency . Note: (1) Routine immunizations with inactivated vaccines are safe in persons with CHH. (2) No serious adverse events have been recorded after immunization with live viral vaccines in individuals of Finnish ancestry with CHH. (3) Individuals with CHH generate humoral and cellular immune response to live viral vaccines. Immunization with live vaccines may be considered in selected individuals with CHH without immunodeficiency or with clinically mild immunodeficiency .

Source: GeneReviews — "Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 5. Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders: Recommended Surveillance

Source: GeneReviews — "Cartilage-Hair Hypoplasia – Anauxetic Dysplasia Spectrum Disorders"