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Keratosis Follicularis Spinulosa Decalvans, X-Linked

OMIM ID:

X-linked recessive
autosomal dominant?

Keratosis Follicularis Spinulosa Decalvans, X-Linked

Alternate Names

keratosis follicularis spinulosa decalvans cum ophiasia
KFSDX
Siemens-1 syndrome

Defective Genes

SAT1

Clinical Characteristics

Ocular Features

There is alopecia of the eyelashes and eyebrows.  The skin of the eyelids is thickened often with an associated chronic blepharitis followed by entropion (ectropion sometimes mentioned).  Photophobia and keratitis with ‘corneal degeneration’ are also features but it is unknown whether these are primary or secondary to trichiasis from the eyelid deformities.  The corneal findings usually precede the scarring alopecia of the scalp.

Systemic Features

Onset is in childhood.  Thickening of skin is generalized especially in the neck, ears, and the extremities with marked involvement of the palms and soles, especially in the calcaneal regions.  Scalp hair may be sparse, often in a streak pattern.  The follicles are inflamed and hyperkeratotic resulting in scarring alopecia.  Carriers have been reported to have dry skin with mild follicular hyperkeratosis and more extensive involvement of the soles.

Genetics

Inheritance

This is a rare disorder with genetic and clinical heterogeneity.  The majority of cases seem to be inherited in an X-linked recessive pattern secondary to mutations in the SAT1 gen located at Xp22.1. 

However, multigenerational families with male to male transmission have also been reported suggesting autosomal dominant inheritance (KFSD; 612843).  However, no associated mutations or loci have been reported for this condition.

 

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

X-linked recessive, carrier mother

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children.  If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome.  However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease.  Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.

Image
Sample pedigree of X-linked recessive inheritance, carrier mother

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.

X-linked recessive, father affected

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children.  If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene.  His sons only receive his Y chromosome and thus are all normal.  However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'.  Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.

Image
Sample pedigree of X-linked recessive inheritance, father affected

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.

Treatment & Management

Retinoids reduce the inflammatory component and lead to cessation of the scalp alopecia.  A decrease in photophobia has also been reported but the clinical basis for this is unknown.

Selected Resources

Web Resources

Publications

Displaying 1 - 3 of 3

Gene dosage of the spermidine/spermine N1-acetyltransferase (SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD)

PubMedID: 12215835

Keratosis follicularis spinulosa decalvans: report of a new pedigree

PubMedID: 8745901

Novel MBTPS2
missense mutation causes a keratosis follicularis spinulosa decalvans phenotype: mutation update and review of the literature

PubMedID: 27663151