OMIM ID:
IFAP (BRESHECK) Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The eyelashes and eyebrow hair is sparse or completely absent. Keratitis with secondary photophobia is often seen during infancy and progresses to corneal vascularization and scarring, sometimes resembling trachomatous disease. Cataracts do not seem to be part of this syndrome unlike some other genodermatoses.
Systemic Features
Dry, scaly skin and alopecia are usually evident at birth. There is marked absence of hair throughout the body. The skin is generally ichthyotic and erythematous, with continuous lamellar desquamation of surface skin. Generalized follicular hyperkeratosis is present on the scalp, dorsal surface of the limbs and on the abdomen. Most patients are completely bald.
In some patients the skin, hair and corneal disease is accompanied by severe internal anomalies such as kidney dysplasia, brain anomalies and mental retardation, Hirschsprung disease, cleft palate, external ear malformations, cryptorchidism, and skeletal deformities, a combination of signs that some have called BRESEK/BRESHECK syndrome. Depending upon how extensive the organ involvement, the prognosis is usually guarded and patients may not live beyond early childhood.
It is uncertain if IFAP refers to a single disorder or if two disorders are involved (see Genetics).
Genetics
Inheritance
This is generally considered to be an X-linked recessive disorder most likely due to mutations in MBTPS2, at least in patients considered to have the BRESHECK condition. Female carrier may have some similar skin and hair signs albeit to a lesser degree than males.
Since the amount of MBTPS2 activity has been shown to vary with different mutations, it is possible that all cases of IFAP with or without the added BRESHECK findings are part of the clinical spectrum of a single disorder (variable expressivity).
Other genodermatoses with severe keratitis are KID syndrome (148210) and Hereditary Mucoepithelial Dysplasia (158310).
Pedigree
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'.
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.
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.