X-linked chromosomal cutis laxa (xrcl) ICD-10: E83.0

The X-linked cutis laxa, also known as occipital horn syndrome, is classified as a mild form of Menkes syndrome. Phenotypically, this syndrome is similar to Cutis laxa of the ARCL2 type.

OHS is inherited X-linked recessively and is based on mutations or deletions or duplications in the gene ATP7A (gene location Xq21.1; Fujisawa C et al. 2019). The ATP4 gene (ATPase Copper Transporting Alpha) encodes an ATPase that controls copper transport through membranes. In about 80 % of the cases, mutations occur, in another 15 % of the cases, a deletion/duplication of several exons of ATP7A is present.

The skin already appears wrinkled and loose at birth. There may be umbilical and inguinal hernias, hypermobility of the joints, osteoporosis. Patients have recurrent urinary tract infections (bladder and ureteral diverticula Kim MY et al 2018) and poorly controlled diarrhea (Canalichio KL et al 2020). Furthermore, delayed motor development is shown as a consequence of muscle hypotonia. Neurological symptoms vary and are often mild, and it is not uncommon to have a mild intellectual deficit. Characteristic and eponymous are exostoses at the back of the head, which usually become clinically evident only at the age of 5-10 years. Other skeletal changes include thoraco-lumbar kyphosis or scoliosis as well as sternal deformities, a long narrow face, often with a high forehead, sloping downward palpebral fissures, high palatal arch, and large protruding ears. The signs of cutis laxa vary in severity. They may increase with age (drooping wrinkles). The pubertal development is normal.

Clinic, detection of an ATP7A mutation

Menkes syndrome; other forms of Cutis laxa; Ehlers-Danlos syndrome

1. Canalichio KL et al (2020) Osseous Metaplasia in a Bladder Diverticulum in a Patient with Mosaic Menkes Disease.Urology 136:238-240.
2. Fujisawa C et al (2019) ATP7A mutations in 66 Japanese patients with Menkes disease and carrierdetection: A gene analysis. Pediatr Int 61:345-350.
3. Kim MY et al (2018) Urological Problems in Patients with Menkes Disease. J Korean Med Sci 34:e4.
4. Sudhahar V et al (2019) Copper Transporter ATP7A (Copper-Transporting P-Type ATPase/Menkes ATPase) Limits Vascular Inflammation and Aortic Aneurysm Development: Role of MicroRNA-125b. Arterioscler Thromb Vasc Biol 39:2320-2337.