Cholesterol metabolsim defect associated with Conradi–Hunerman–Happle syndrome

Abstract

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). The 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. Ultrastructural 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-3beta-ol of 6.8 microg/mL (normal, 0.01-0.10 microg/mL) and an increase in 8-dehydrocholesterol (5.1 microg/mL) (normal, <0.10 microg/mL).

Genetic syndrome with ichthyosis: congenital ichthyosis, follicular atrophoderma, hypotrichosis, and woolly hair; second report

“…In older children generalized atrophoderma mainly involving the hair follicles and pigmentary disturbances are noted. Other features include stippled calcifications of the area of enchondral bone formation, asymmetric shortening of legs 5,6 . Major findings of this syndrome were absent in our patient.…”

“…These lesions were present on the extensor surfaces of the hands of our patient. Follicular atrophoderma has been described repeatedly in association with other genetically determined abnormalities such as X‐linked dominant chondrodysplasia punctata and Bazex syndrome 3,5 . We ruled out these syndromes because there were no characteristic manifestations.…”

Characterization of mutations in 22 females with X-linked dominant chondrodysplasia punctata (Happle syndrome)

“…Blood or skin samples were obtained for molecular studies after informed consent and protocols approved by the appropriate institutional human subjects review boards. Clinical descriptions of Patients 2 and 10 have been reported by DiPreta et al 11 and Sutphen et al, 12 respectively. For two of the patients, no clinical information was available.…”

Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis

“…− not reported atrophoderma, sparse hair), a typical facies with a flat, depressed nasal bridge, frontal bossing and generally normal intelligence [20][21][22][23][24][25][26][27][28]. The random pattern of X inactivation explains the asymmetrical or patchy involvement, the variable intra-and interfamilial expressivity and the lack of clear genotype/phenotype correlation in affected girls [1,29].…”