Cholesterol metabolsim defect associated with Conradi–Hunerman–Happle syndrome
Authors: DiPreta Edward A. , Smith Kathleen J. , Skelton Henry 
Published: March 2003

We present a 6‐week‐old black girl with Conradi–Hunerman–Happle syndrome (CHS). The mother had no past medical history of illness, and the pregnancy progressed normally to a spontaneous vaginal delivery at 36 weeks. There was no known significant family history. A diagnosis of chondrodysplasia punctata was made at birth from physical examination and X‐ray findings. On physical examination at 6 weeks, a koala face, a saddle nose, and a right‐sided cataract were noted (Fig. 1a,b). There was unilateral left‐sided ichthyosis well demarcated at the midline, with whorled brown fine scale following Blashko's lines on the patient's right side. Orthopedic complications were bilateral but were more pronounced on the left side. There was bilateral shortening of the humerus, with polydactyly of the right hand, arachnodactyly of the left fingers, bilateral clubbing, and mild contractures of the feet. X‐Rays showed multiple calcifications along the spine, proximal and distal femoral epiphysis, and proximal humeral epiphysis (Fig. 2).Six‐week‐old black girl with X‐linked dominant chondrodysplasia punctata (XCDP2). The patient has a koala face, a saddle nose (a), and a right‐sided cataract (b). There is unilateral left‐sided ichthyosis well demarcated at the midline. The ichthyosis consists of whorled brown fine scale following Blashko's lines on the patient's right side, including the abdomen, thigh, upper back, and upper and lower extremities. There is bilateral shortening of the humerus, polydactyly of the right hand, arachnodactyly of the left fingers, bilateral clubbing, and mild contractures of the feetimageX‐Rays showing multiple calcifications along the spine, proximal and distal femoral epiphysis, and proximal humeral epiphysis in the patient with X‐linked dominant chondrodysplasia punctata (XCDP2)imageThe patient was treated with emollients (aquaphor) twice daily with continuing improvement in ichthyosis. The clubbed feet were treated with splinting and the polydactyly was corrected by surgery. Ophthalmology was to follow the patient for her right‐sided cataract. At the patient's 4‐month follow‐up, the ichthyosis showed a marked improvement with some residual hypo‐ pigmented atrophoderma noted. The distribution remained unchanged.Biopsies taken of ichthyotic lesions showed compact hyperkeratosis and follicular plugging. Vesicles within the stratum corneum contained amorphous material (Fig. 3a,b). The granular cell layer was thickened with retained oval nuclei. The epidermal and adnexal epithelium were disorganized. Increased apoptotic/dyskeratotic keratinocytes were seen within the epidermis, but were most evident within the follicular epithelium.(a, b) Sections from biopsy specimens of the X‐linked dominant chondrodysplasia punctata (XCDP2) patient showing compact hyperkeratosis and follicular plugging. Vesicles within the stratum corneum contain amorphous material. The granular cell layer is thickened with retained oval nuclei. The epidermal and adnexal epithelium are disorganized. Increased apoptosis/dyskeratosis are seen within the epidermis, but are most evident within the follicular epithelium (400×, 400×)imageUltrastructural studies showed saccular dilations of the acellular space within the stratum corneum. These acellular spaces were filled with unprocessed lamellated pleated sheets and vesicle complexes and processed lamellae. Dyskeratotic cells were seen within the stratum spinosum.Red blood cell (RBC) plasmalogen levels and polyunsaturated fatty acids (PUFA), including decosahexaenoic acid (DHA), were within normal limits. Plasma very long chain fatty acids (VLCFA), including C26 : 0/C22 : 0 ratios, phytanic and pristanic acids, plasmalogen, and phytanic/pristanic ratios, trihydroxycholestanic acid (THCA) and dihydroxycholestanoic acid (DHCA) including their ratios, THCA/cholic acid and DHCA/chenodeoxycholic acid, and PUFAs including DHA were within normal limits. Urine organic acids and piecolic acid were within normal limits. Despite these normal values, there was an increase in cholest‐8(9)‐en‐3β‐ol of 6.8 μg/mL (normal, 0.01–0.10 μg/mL) and an increase in 8‐dehydrocholesterol (5.1 μg/mL) (normal, <0.10 μg/mL).