A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2.

OBJECTIVE: The classic triad, which defines IFAP syndrome, is ichthyosis follicularis, alopecia, and photophobia. It is a rare X-linked genetic disorder characterized by multiple congenital anomalies with variable severity, caused by pathogenic variants in the MBTPS2 gene, which encodes a zinc metalloprotease that is essential for normal development. This study aimed to report a case of a Brazilian patient with IFAP syndrome presenting skeletal anomalies, which is a rare finding among patients from different families. CASE DESCRIPTION: We describe a male proband with IFAP syndrome showing severe ichthyosis congenita, cryptorchidism, limb malformation, and comprising the BRESHECK syndrome features. Using whole-exome sequencing, we identified a rare missense variant in hemizygosity in the MBTPS2 gene, which had not been identified in other family members. COMMENTS: This is the first diagnosis of IFAP syndrome in Brazil with a molecular investigation. The present case study thus expands our knowledge on the mutational spectrum of MBPTS2 associated with IFAP syndrome.

Developmental cataract in congenital ichthyosis.

A teenage boy who was previously diagnosed to have congenital ichthyosis presented to the eye clinic with complaints of gradually decreasing vision in both eyes since childhood. The best-corrected distance visual acuity was 20/125 in the right eye and 20/40 in the left eye. Clinical examination revealed developmental cataracts in both eyes. He underwent cataract surgery in the right eye and visual acuity improved to 20/25. Hence, we conclude that congenital ichthyosis can be associated with developmental cataracts. Cataract surgery helps in restoring vision in those with visually significant cataracts.

Ichthyosis, petechiae, and arthrogryposis in a neonate.

Gaucher disease is a rare lysosomal storage disorder caused by a deficiency in glucocerebrosidase. This enzyme deficiency leads to the accumulation of toxic metabolites in various organs. Multiple subtypes of this disease have been described; however, the perinatal-lethal form is extremely rare and challenging to diagnose. We present a case of a newborn girl with ichthyosis, petechiae, and arthrogryposis, later found to be homozygous for a pathogenic variant of the glucocerebrosidase gene. This case highlights the potential role of dermatologists in the recognition of this rare disease.

Severe Bilateral Ectropion in Lamellar Ichthyosis: A Case Report.

BACKGROUND Lamellar ichthyosis is a rare type of hereditary ichthyosis disease that is responsible for generalized dry skin and severe scaling. Congenital ectropion and eclabium are often associated with this condition. The ectropion can cause many ophthalmologic complications, mostly due to corneal exposure caused by the lack of eyelid cleft closure. The corneal exposure can cause ulceration and even corneal perforation leading to phthisis bulbi. CASE REPORT We report the case of a North African newborn baby diagnosed with congenital lamellar ichthyosis responsible for severe skin scaling, eclabium, and bilateral ectropion of both the upper and lower eyelids. The therapeutic care of the baby was ensured by a collaboration between ophthalmologist and dermatologist. The newborn was treated by oral acitretin and skin emollients for his dermatological conditions and on the ophthalmological level he was put on lubricating and moisturizing eye drops and gel, associated with daily repeated eyelid massage. The evolution after 6 months of treatment showed excellent results on both the dermatological and the ophthalmological level. CONCLUSIONS At the stage of cicatricial ectropion in lamellar ichthyosis, the management is mainly based on a chirurgical approach. However, if the ectropion is managed early enough, the treatment could be medical, which is much easier, produces very good results, and prevents the progression toward eyelid fibrosis and its associated complications that can make the management of the ectropion much harder.

Congenital lamellar ichthyosis complicated with erosive pseudo pustulosis: A rare clincal entity. About a case and review of the literature.

INTRODUCTION: Lamellar ichthyosis is a rare congenital disorder that can be encountered by plastic surgeon in a daily practice. Its clinical diagnosis makes it an significant pathology to identify and to know how to treat. MATERIAL AND METHODS: We report the case of a patient suffering from lamellar ichthyosis complicated by erosive pseudo pustulosis of the scalp. Our treatment protocol with two intra-lesional delayed-corticoids (Kenacort ®) injections three months apart showed significant clinical improvement of the lesions. DISCUSSION: Congenital lamellar ichthyosis regroups various clinical presentations. Most of the therapeutic strategies described in the literature involve local and systemic treatments, weighing on patients and leading to modest results. Surgical treatment or hyaluronic injections have also been reported but they raise problematics regarding morbidity and efficiency. CONCLUSION: Our therapeutic strategy by two Kenacort ® injections three months apart is simple, reproductible and has shown efficiency in the treatment of our patient suffering from congenital lamellar ichthyosis complicated with erosive pseudo pustulosis of the scalp.

Evaluation of neurodevelopmental symptoms in 10 cases of neonatal ichthyosis and sclerosing cholangitis syndrome.

Neonatal ichthyosis and sclerosing cholangitis (NISCH) syndrome is an extremely rare entity with only 19 patients described in the literature. We report an extended family with the disorder and investigate the association of neurodevelopmental symptoms. Patients with CLDN1 mutations, and specifically « the Moroccan¼ c.200_201delTT deletion, may be an increased risk for neurodevelopmental symptoms such as learning disabilities, mental retardation, and language delay.

Juvenile idiopathic arthritis in Harlequin ichthyosis, a rare combination or the clinical spectrum of the disease? Report of a child treated with etanercept and review of the literature.

BACKGROUND: Harlequin ichthyosis (HI) is the most severe phenotype of autosomal recessive congenital ichthyosis. Juvenile Idiopathic Arthritis (JIA) represents a heterogenous group of disorders all sharing the clinical manifestation of chronic arthritis. Association of HI and chronic arthritis has been reported in few cases. CASE PRESENTATION: We report the case of a child with HI who developed a severe form of chronic polyarthritis during the first years of life, treated with repeated multiple joint injections, methotrexate and etanercept with good response and without any adverse events. CONCLUSION: The reported case and the literature review highlighted the presence of a peculiar severe seronegative polyarthritis with early onset in a series of patients with HI, suggesting that polyarthritis may be a specific manifestation of HI, rather than a rare combination of two separate conditions.

Combined medical and surgical management for cicatricial ectropion in lamellar ichthyosis: A report of three cases.

Ichthyosis is a rare inherited skin disorder characterized by abnormal keratinization of the epidermis. Cicatricial ectropion is the most common ophthalmic feature of congenital ichthyosis. Progressive subepithelial cicatrization and abnormal cornification of eyelid skin cause progressive ectropion in both eyelids, leading to lagophthalmos and corneal exposure. Surgical correction of cicatricial ectropion in these cases is challenging with unsatisfactory results. Proper processing of the donor and recipient site with lubricants and topical retinoids before surgery makes grafting easier and its survival better. We present three cases of lamellar ichthyosis with cicatricial ectropion managed with combined preoperative topical therapy followed by surgery. All patients had extremely good surgical outcomes, with none of them requiring repeat surgery.

Oral manifestations of lamellar ichthyosis in association with rickets.

Lamellar ichthyosis (LI) is a rare genetic condition that affects the skin, with an incidence of less than 1:300 000 in different parts of the world. This report describes a case of a 5-year-old girl with LI and rickets presenting with premature loss of 51, 52, 61, 62 and 71, grade II mobility in 72, 73, 81, 82 and 83 along with loss of supporting bone with 53, 63, 72, 73, 82 and 83. This is the first report describing oral manifestations of this combination of LI and rickets.

Sight-threatening Complication of Cicatricial Ectropion in a Patient with Lamellar Ichthyosis - Case Report.

We report a case of lamellar ichthyosis and sight-threatening complications of cicatricial ectropion in an adult male patient which was surgically managed with tectonic penetrating keratoplasty. We present a case of autosomal-recessive lamellar ichthyosis in a 47-year-old man who was referred to our outpatient eye clinic for treatment of primary keratouveitis of the right eye with keratolysis and exudation in the anterior chamber. A diagnosis of cicatricial ectropion with serious lagophthalmos was established on examination. The patient underwent tectonic penetrating keratoplasty, cataract extraction, and intra-ocular lens placement with no perioperative complications. The patient was subsequently treated with oral fluconazole 200 mg once daily for 12 days due to a positive fungal culture for Candida albicans and systemic oral acyclovir 250 mg 3 times per day for 12 days as prophylaxis for a labial herpetic infection. Post-operative complications included corneal rejection and nonhealing neurotropic epithelial defect of the graft. Long-term treatment with topical cyclosporine (Ikervis®) and dexamethasone led to resolution of the corneal rejection. Lubrication with artificial tears containing hyaluronic acid, perfluorohexyl octane (Evotears®), and vitamin A ointment led to symptomatic relief of dry eye disease. The patient was referred to a dermatologist and was started on systemic retinoid acitretin at a dose of 0.5 mg/kg per day. Ten months after surgery, the patient's visual acuity was 0.1 based on the Snellen chart and the corneal graft was stable. Infection in the cornea can rapidly progress to corneal melting in patients with severe cicatricial ectropion. A good patient outcome depends on the interdisciplinary approach to patient management by the ophthalmologist, dermatologist, and plastic surgeon.

Phenotypic suppression of acral peeling skin syndrome in a patient with autosomal recessive congenital ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) manifests with generalized scaling often associated with generalized erythema. Mutations in at least 13 different genes have been reported to cause ARCI. Acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder manifesting with peeling over the distal limbs and dorsal surfaces of hands and feet. APSS is mostly due to mutations in TGM5, encoding transglutaminase 5. Both ARCI and APSS are fully penetrant genetic traits. Here, we describe a consanguineous family in which one patient with mild ARCI was found to carry a homozygous mutation in ALOXE3 (c.1238G > A; p.Gly413Asp). The patient was also found to carry a known pathogenic homozygous mutation in TGM5 (c.1335G > C; p.Lys445Asn) but did not display acral peeling skin. Her uncle carried the same homozygous mutation in TGM5 but carried the ALOXE3 mutation in a heterozygous state and showed clinical features typical of APSS. Taken collectively, these observations suggested that the ALOXE3 mutation suppresses the clinical expression of the TGM5 variant. We hypothesized that ALOXE3 deficiency may affect the expression of a protein capable of compensating for the lack of TGM5 expression. Downregulation of ALOXE3 in primary human keratinocytes resulted in increased levels of corneodesmosin, which plays a critical role in the maintenance of cell-cell adhesion in the upper epidermal layers. Accordingly, ectopic corneodesmosin expression rescued the cell-cell adhesion defect caused by TGM5 deficiency in keratinocytes as ascertained by the dispase dissociation assay. The present data thus provide evidence for phenotypic suppression in a human hereditary skin disorder.

Successful correction of ichthyosis-related ectropion by autografts.

Ectropion is a rather frequent complication of ichthyosis with negative functional and esthetic impact. Lid surgery can provide significant improvement. We report on a series of four ichthyosis patients with ongoing bilateral eye problems despite intense medical treatment (mean age 27.8 ± 14.1 years). All patients suffered from lagophthalmos. Two of the patients had only lower lid ectropion. In two of the patients' ectropion was forming on the upper lid in addition to the lower lid when closing the eye. In three of four patients, ectropion was repaired by skin grafts from the supraclavicular region. In a child with lower and upper lid ectropion prepuce was used for repair surgery. At the end of the follow-up period of about 23.0 ± 12.7 months, none of the patients revealed lagophthalmos or corneal exposure. No intraoperative or postoperative complications have been observed in our patients. Ichthyosis patients with ectropion resistant to medical treatment, benefit from surgical treatment with full layer autografts. In boys, prepuce can be successfully used as autograft.

Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review.

BACKGROUND: Harlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge. CASE PRESENTATION: We describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate. CONCLUSIONS: The association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.

Increased melanocytic nevi and lentigines in two patients with harlequin ichthyosis.

An increased number of melanocytic nevi and lentigines have been reported in patients with two types of autosomal recessive congenital ichthyosis (ARCI): lamellar ichthyosis and nonbullous congenital ichthyosiform erythroderma. These melanocytic lesions may have clinical and dermoscopic features of atypia, necessitating close surveillance. Here, we report two interesting cases of pediatric patients with harlequin ichthyosis (HI) who developed increased melanocytic nevi and lentigines. These cases are unique in that the patients presented at a younger age and one patient had a darker skin phototype than previously described in the literature.

Management of ocular manifestations of autosomal recessive congenital ichthyosis 4B, harlequin type, in the perinatal period.

Autosomal recessive congenital ichthyosis (ARCI4B [OMIM #242500]), also known as harlequin ichthyosis, presents at birth with extreme hyperkeratosis and thick-fissured plaques, leading to tightness of the skin around the eyes, mouth, ears, chest, abdomen, and extremities. Ocular manifestations include cicatricial ectropion and exposure keratitis. We present 2 infants with ARCI4B and cicatricial ectropion who were managed with aggressive nonsurgical therapy. Both infants avoided severe ocular sequelae and maintained corneal clarity, highlighting that management of exposure keratopathy with frequent ophthalmic ointment application can prevent severe ocular surface pathology in ARCI4B.

Case Report: Corneal Ulceration from Bilateral Ectropion Due to Congenital Ichthyosis.

SIGNIFICANCE: Ichthyosis is a group of heterogenous inherited skin disorders characterized by abnormal cornification and keratinization of the skin. Autosomal recessive congenital ichthyosis presents with severe lagophthalmos and cicatricial ectropion of both upper and lower lids. Chronic corneal exposure from lid abnormalities may lead to ulcerative keratitis or corneal perforation. PURPOSE: The case highlights a rarely seen condition that presents with potentially serious ocular complications and vision loss. Corneal complications may be avoided or managed with moisture goggles, corneal vaulting with scleral lenses, topical therapeutics, amniotic membrane, and surgical lid repair. CASE REPORT: A 25-year-old woman presented with a painful right eye for 1 week. She had a medical history of autosomal recessive congenital ichthyosis. Her ocular adnexa revealed bilateral lagophthalmos and cicatricial ectropion of both upper and lower lids. The slit lamp of examination revealed an injected eye with corneal ulcer with hypopyon in the right eye and quiet eye with corneal scarring in the left eye. The patient was treated with topical moxifloxacin and polymyxin B sulfate/trimethoprim as well as in-office homatropine 5% in the right eye. The keratitis was treated to resolution, and the patient referred for consultation on lid repair. CONCLUSIONS: Chronic corneal exposure from autosomal recessive congenital ichthyosis may lead to severe dry eye, ulcerative keratitis, or perforation. Patients should be monitored carefully for corneal disease, educated on methods and devices to protect the corneal surface, and referred for surgical repair if indicated. Although rare, this condition presents unique findings that may be visually devastating. Awareness of the condition, as well as the various clinical presentations and appropriate management necessary, will prove beneficial to the patient.