Send to

Choose Destination

NSDHL-Related Disorders.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.
2011 Feb 1 [updated 2018 Oct 25].

Author information

Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
Department of Human Genetics, Philipps-Universität, Marburg, Germany



The NSDHL-related disorders include: CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked condition that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked disorder that affects males. CHILD syndrome is characterized by unilateral distribution of ichthyosiform (yellow scaly) skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life; new lesions can develop in later life. Nail changes are also common. The heart, lung, and kidneys can also be involved. CK syndrome (named for the initials of the original proband) is characterized by mild to severe cognitive impairment and behavior problems (aggression, attention deficit hyperactivity disorder, and irritability). All affected males reported have developed seizures in infancy and have cerebral cortical malformations and microcephaly. All have distinctive facial features, a thin habitus, and relatively long, thin fingers and toes. Some have scoliosis and kyphosis. Strabismus is common. Optic atrophy is also reported.


The diagnosis of CHILD syndrome is established in a proband by identification of an NSDHL pathogenic variant that results in loss of functional NSDHL protein. The diagnosis of CK syndrome is established in a proband by identification of a "hypomorphic" NSDHL pathogenic variant that results in partial loss of functional NSDHL protein.


Treatment of manifestations: CHILD syndrome. No one therapy described to date appears to ameliorate the cutaneous findings for every reported individual with CHILD syndrome. Lactic acid 12% skin creams or lotions can reduce itching, and urea skin creams can reduce dryness. Treatment of an inflammatory nevus by grafting skin obtained from a contralateral unaffected region has been successful. Oral aromatic retinoids (etretinate) used to ameliorate cutaneous symptoms have been found to be of limited use and not well tolerated. Topical statins may be beneficial for the treatment of inflammatory nevus. Scoliosis and joint contractures are treated with braces and/or corrective surgery. CK syndrome. Behavior modification and/or drug therapy to control aggression and help with ADHD symptoms; antiepileptic drugs to control seizures. Surveillance: CHILD syndrome. Monitoring for new cutaneous lesions and musculoskeletal deformities such as scoliosis and joint contractures. CK syndrome. Monitoring for the effectiveness of AEDs in controlling seizures and for the development of scoliosis/kyphosis.


The NSDHL-related disorders are inherited in an X-linked manner. No affected male has reproduced. CHILD syndrome is usually male lethal during gestation. Affected females have a 50% chance of transmitting the NSDHL pathogenic variant in each pregnancy; however, the expected live born distribution of persons at risk for CHILD syndrome is 33% unaffected females, 33% affected females, and 33% unaffected males. CK syndrome is diagnosed in males. Heterozygous females have a 50% chance of transmitting the NSDHL pathogenic variant in each pregnancy; males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will have normal physical features, intellect, and brain imaging but may display behavioral problems such as irritability and aggression. Testing of at-risk female relatives and prenatal testing for pregnancies at increased risk for an NSDHL-related disorder are possible if the pathogenic variant has been identified in the family.

Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center