CK syndrome

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The NSDHL gene at Xq28 codes for the 373 amino acid pro-peptide to sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating. This allows the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis.

3-beta-hydroxysteroid-4-alpha-carboxylate + NADP+ => 3-oxosteroid + CO2 + NADPH

Defects in this gene are a cause of congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome, OMIM:308050. This is manifest by:

  • Usually male lethality
  • In females manifestations can vary due to mosaicism (photos of typical appearance[1]:
    • Congenital, unilateral, ichthyosisform erythroderma
      • Striking lateralization and sharp midline demarcation for reasons not understood
      • Ipsilateral limb defects
        • Hypoplasia of digits or ribs
        • Sometimes complete amelia
      • Trucal hypoplasia of the body and scoliosis.

The main differential diagnosis is Conradi-Hunermann syndrome which has bilateral skin disease and is caused by CDPX2 gene defects that also results in accumulation of 8-dehydrocholesterol and 8(9)-cholestenol. The other disorders involving enzyme defects in the post-squalene cholesterol biosynthesic pathways are Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, and hydrops-ectopic calcification-moth-eaten skeletal dysplasia.

Specific treatment of the skin condition directed at inhibiting toxic cholesterol precursors is possible with:

  1. Simvastatin and cholesterol ointment[2] (any statin and cholesterol should do)
  2. Ketoconazole orally or cream[3]

Acitretin has also been reported to control symptoms[1].

Other defects in NSDHL are a cause of CK syndrome OMIM:300831. In males this typically presents as:

  • Microcephaly
  • Severe intellectual disability
  • Seizures
  • Optic disk atrophy
  • Skeletal abnormalities, and minor facial anomalies, including a high nasal bridge, strabismus, and micrognathia.
  • Some cases have[4]:

References