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).