Acknowledgement of Conradi-Hünermann-Happle Syndrome has not been added yet.

The exact prevalence of CHHS is hard to determine due to its rarity. It is estimated to affect 1 in every 100,000-200,000 children born genetically female. About 95% of cases are in children born genetically female, as the condition is typically lethal in genetic males before birth.

Name	Abbreviation
X-linked dominant chondrodysplasia punctata 2	CDPX2
Conradi-Hünermann syndrome
Happle syndrome
Chondrodystrophia calcificans congenita

CHHS is caused by mutations in the EBP gene located on the X chromosome, which encodes the emopamil-binding protein (EBP) that acts as a delta8-delta7-sterol isomerase enzyme that plays a key role in the final steps of cholesterol biosynthesis. Loss of EBP function leads to the accumulation of cholesterol precursors and decreased levels of cholesterol in skin, plasma and other tissues. The condition follows an X-linked dominant inheritance pattern (see RareShare Guide on Genetic Inheritance) for which females are predominantly affected.

The clinical features of CHHS can vary significantly but typically include the following:

1. Skin Manifestations:

   • Ichthyosis (dry, scaly skin), linear or whorled patches of scaling skin (Blaschko’s lines).

   • Pigmentary changes and cicatricial alopecia (scarring hair loss).

   • Follicular atrophoderma (small, depressed, or scar-like lesions on the skin).

2. Skeletal Abnormalities:

   • Punctate calcifications in the cartilage (chondrodysplasia punctata).

   • Asymmetric shortening of bones.

   • Scoliosis or kyphosis (irregular spine curvature).

   • Joint contractures, short stature, and developmental delays.

3. Ocular Features:

   • Cataracts or lens opacities, which may develop in infancy or early childhood and cause visual impairment.

   • Microphthalmia (abnormally small eyes) and optic nerve defects in some cases.

4. Other Systemic Features:

   • Craniofacial abnormalities, such as a broad forehead and epicanthal folds.

   • Coarse, sparse hair and dental or nail abnormalities.

   • Hearing loss (sensorineural), may be present in some individuals.

Diagnosis is based on clinical examination, family history and characteristic findings such as skin lesions, skeletal abnormalities, and cataracts. Genetic testing for mutations in the EBP gene is confirmatory. Other diagnostic approaches include:

• Plasma sterol analysis:  Elevated levels of cholesterol precursors 8(9)-cholestenol and 8-dehydrocholesterol.

• Imaging studies:  X-rays can reveal skeletal abnormalities, including punctate calcifications.

Genetic testing:  To identify mutations in the EBP gene and confirm the diagnosis.

Diagnostic tests of Conradi-Hünermann-Happle Syndrome has not been added yet

There is no cure for CHHS, and treatment is supportive, focusing on managing symptoms and preventing complications:

1. Dermatological Care:

   • Topical emollients and moisturizers to manage skin dryness and scaling.

   • Regular skin exams to monitor for changes and prevent infections due to fragile skin.

2. Orthopedic Management:

   • Monitoring and managing skeletal issues such as scoliosis, joint contractures, and developmental delays.

   • Physical therapy to improve mobility and flexibility.

   • Surgical intervention may be necessary for severe skeletal deformities or joint issues.

3. Ophthalmologic Care:

   • Regular eye examinations to monitor for cataracts and other ocular abnormalities.

   • Cataract surgery if necessary to improve vision.

4. Hearing and Developmental Support:

   • Audiological assessments to monitor for hearing loss and the use of hearing aids if needed.

   • Developmental support and early intervention to address developmental delays.

5. Genetic Counseling:

   • Families affected by CHHS should seek genetic counseling to understand the inheritance pattern and recurrence risk.

Ongoing monitoring of the condition is crucial for managing complications.

 

The prognosis for individuals with CHHS varies. With early diagnosis and appropriate treatment, many affected individuals can lead a relatively normal life. However, the severity of the symptoms can range from mild to severe, with some individuals experiencing significant developmental and physical challenges. Early interventions and regular follow-ups can improve outcomes and quality of life.

Tips or Suggestions of Conradi-Hünermann-Happle Syndrome has not been added yet.

1. J. Cañueto, et al. (2012). Clinical, molecular and biochemical characterization of nine Spanish families with Conradi–Hünermann–Happle syndrome: new insights into X‐linked dominant chondrodysplasia punctata with a comprehensive review of the literature. British Journal of Dermatology, 166(4), 830–838. https://doi.org/10.1111/j.1365-2133.2011.10756.x.

2. Kelley RI, Herman GE. (2001). Inborn errors of sterol biosynthesis. Annu Rev Genomics Hum Genet. 2, 299-341. https://doi.org/10.1146/annurev.genom.2.1.299.

3. Orphanet:  X-linked dominant chondrodysplasia punctata.

4. National Organization for Rare Disorders (RareDiseases.org):  Conradi–Hünermann syndrome.