IFAP syndrome

IFAP syndrome: Description, Causes and Risk Factors:IFAP syndromeIFAP syndrome is a rare genetic disorder characterized by ichthyosis and alopecia from birth and sometimes accompanied by short stature, intellectual disability, and seizures that develop in the first few years of life. Photophobia may also be present in the first year of life or appears in infancy or early childhood. Its mode of inheritance is X-linked recessive, thus mostly affecting males. Affected or carrier females may display some of its clinical features.The IFAP syndrome is a rare X-linked genetic disorder reported in nearly 40 patients so far.The disorder results from mutations in the MBTPS2 gene that impairs cholesterol homeostasis and the ability to cope with endoplasmic reticulum stress. This gene encodes an intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with IFAP syndrome. IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.A recessive X-linked pattern of inheritance has been established for IFAP. Therefore, the risk for a female carrier to have an affected son is 50%. The mutation might also arise in the patient's de novo.Recently, a mother and daughter, and 2 unrelated female patients with an IFAP syndrome were reported. They did not have linear distribution of skin lesions, suggesting an autosomal dominant mode of transmission. Thus, besides X-linked recessive inheritance, an autosomal dominant mode of inheritance could be present.Life expectancy in patients with IFAP syndrome can vary from death in the neonatal period to normal surviving. Cardiopulmonary complications were the main cause of death.Symptoms:The main symptoms are dry, scaly skin, absence of hair and excessive sensitivity to light (photophobia). Additional features include short stature, mental retardation, seizures and a tendency for respiratory infections.Other clinical features associated with IFAP syndrome consist of short stature, dysmorphic features such as frontal bossing, choanal atresia, and large ears. Intestinal anomalies such as omphalocele, Hirschsprung disease, congenital aganglionic megacolon, stenosis of the small intestine, and inguinal hernia, renal, cardiac and vertebral anomalies, and cleft hands have been reported. Recurrent infections are often noted in IFAP syndrome. External genitalia are almost always normal; few cases presented with cryptorchidism and one with a hypospadias. Dental development is normal.Diagnosis:Diagnosis is based on appearance and family history. The diagnosis is confirmed by carefully examining the skin and ruling out other malignancies.Skin histopathology is non-specific and consists of dilated hair follicles with keratin plugs extending above the surface of the skin, decreased or absent sebaceous glands and normal sweat glands. Transverse section of scalp biopsy can reveal abortive sebaceous glands in hair follicles. The number of total hair follicles is not significantly decreased suggesting that the pilosebaceous hypoplasia might arise from impaired maturation during hair follicle morphogenesis.On electron microscopy moderate spongiotic changes associated with partial disruption of the intercellular bridges, decreased desmosomes in number and size, and some dyshesion of the cells could be seen. Examination of the cornea with EM can show reduced number of desmosomes in the corneal epithelium, dispersed bundles of tonofilaments and dilated intercellular gaps with segregated desmosome remnants.Treatment:IFAP syndrome can be treated using topical keratolytics, emollients and urea preparations. A moderate response to acitretin therapy has been noted in some patients. Intensive lubrication of the ocular surface is essential. A moderate response to acitretin therapy at a dose of 0.3 to 1 mg/Kg/day with improvement in cutaneous features and corneal erosions but no changes regarding alopecia and photophobia have been noted in some patients. Seizures must be treated accordingly.NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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