Laryngeal features in Lipoid proteinosis: a systematic review and meta-analysis of individual participant data.

PURPOSE: Lipoid proteinosis (LP) or Urbach-Wiethe disease (OMIM 247100) is a rare syndrome characterised by early vocal folds infiltration and subsequent multi-organ involvement. LP is often unrecognised and its associated hoarseness is overlooked. The main objective of the study was to investigate hoarseness in LP and implement a diagnosis among otolaryngologists. METHODS: PubMed/MEDLINE and OMIM databases were systematically searched. Authors concentrated the search on published articles starting from the discovery of the pathogenesis of LP by Hamada et al. in 2002. Only cases in which a diagnosis was reported both clinically and through biopsy and/or genetic molecular testing were included. Characteristics of the LP cases were extracted from each included study. Results were obtained through Generalized Estimating Equations. RESULTS: The search strategy yielded 217 articles, of which 74 (34.1%) met the selection criteria. A total of 154 cases were included. Hoarseness was described in all LP cases and clearly stated as the onset symptom in 68.8%. The onset was on average at 19 months of age (CI: 3.00-20.00), while the mean age at diagnosis was 15 years (CI: 10.00-30.00). Therefore, the diagnostic delay amounted to 13.42 years (CI: 8.00-23.83). Hoarseness alone was responsible for an LP diagnosis in only 14.3% of cases. In 43.5% of cases, genetic analysis of the ECM1 gene was performed and exon 6 was the most frequently altered portion. CONCLUSION: Analysing the largest number of published cases, the study underlined that hoarseness is the key symptom for diagnosing LP since early childhood, though frequently overlooked.

Pediatric Voice Disorders from the Perspective of Rare Diseases.

OBJECTIVE: This study aims to present rare pediatric voice disorders, which are usually reported as case reports in the literature, with their clinical features, treatment options, and prognosis, and to emphasize clinical findings that may be associated with rare diseases. METHODS: The clinical records of the pediatric patients presented with dysphonia were reviewed between 2014 and 2019. The terminology "rare disease" is used to describe diseases where the average prevalence thresholds are between 40 to 50 cases/100,000 people. Age, gender, symptoms, laryngeal examination findings, histopathological results, treatment modalities and follow-up results of rare laryngeal pathologies were reviewed. RESULTS: 274 children were diagnosed with and treated for voice disorders at our institution. Seven patients were identified with rare laryngeal pathologies. Four patients diagnosed with lipoid proteinosis, two patients with neurofibroma and one patient with amyloidosis. One patient was known to have neurofibromatosis type-1, while the others did not have any previously diagnosed diseases, dysphonia was the initial clinical presentation. CONCLUSION: There are some clues that bring to mind rare entities. Firstly, these patients generally present with various systemic manifestations. Secondly, if there is any discrepancy between voice quality and endoscopic laryngeal examination, the diagnosis should be reconsidered. Thirdly, in the case of the prolonged dysphonia recalcitrant to treatment, the clinician should reassess the treatment or the diagnosis.

Lipoid Proteinosis: A Rare Cause of Hoarseness.

Lipoid proteinosis is a rare cause of voice problems. Hoarseness is often the first clinical manifestation of this disorder and can present years before any other symptom. Therefore, it is very important as an otorhinolaryngologist to be familiar with the main characteristics of this disease. We present a case report and a review of current literature to provide a concise overview of this frequently missed diagnosis.

[An atypical case of lipoid proteinosis]. / Un cas atypique de protéinose lipoïde.

The lipoid proteinosis is a rare autosomic recessive genodermatosis characterized histologically by deposits of hyaline-like eosinophilic material of characteristic distribution. We herein report the case of a 56-year-old man admitted for progressive aggravated dementia associated with a late-onset dysphonia. Histologic examination of cutaneous and laryngeal biopsies showed deposits of an amorphous and eosinophilic material arranged around vessels, and adnexal structures, stained by PAS and congo red negative. The detection of a mutation in the ECM1 gene confirmed the diagnosis of lipoid proteinosis of atypical clinical presentation.

The eye and the skin in nonendocrine metabolic disorders.

As metabolism is controlled by the input of genes and the environment, metabolic disorders result from some disturbance in the interaction between genes and environmental factors. Many metabolic disorders consist in congenital enzyme deficiencies, also known as "inborn errors of metabolism," that may be disabling or cause severe illness and death and are predominantly inherited in an autosomal recessive fashion. The deposit in cells and tissues of storage substances from errors in metabolic processes may produce a wide variety of disorders affecting different organs and functions, with different degrees of severity, and often present around the time of birth or early childhood. Distinctive ocular and skin manifestations accompany many metabolic diseases and may provide clues for their diagnosis and evolution.

Urbach-Wiethe disease in a young woman: A case report.

Urbach-Wiethe disease (lipoid proteinosis) is an autosomal recessive disorder that is characterized by a general thickening of the skin and mucous membranes. We report the case of a 22-year-old woman with lipoid proteinosis who presented with hoarseness, poor dentition, and skin lesions, and we discuss the management of this rare disease.

Vocal fold hyalinosis in Urbach-Wiethe disease, a rare cause of hoarseness.

BACKGROUND: Lipoid proteinosis is an autosomal recessive disorder characterized by hyalin deposits in the skin and mucosa of the upper aerodigestive tract; currently, no treatment exists. Nearly all patients experience hoarseness and speech difficulties, due to hyalin deposition in the vocal folds and diminished mobility in infiltrated lips, tongue, and palate. METHODS: We describe a patient with extensive hyalin plaques on the vocal folds, which resulted in near-aphonic hoarseness. Hyalin deposits in the vocal folds and skin were treated with laser resection. RESULTS: Both the vocal folds and skin improved in appearance, with smoother surface epithelium. However, the patient's speech remained impaired, due to extensive hyalin plaques in the mouth, tongue, and lips. The voice improved only temporarily. CONCLUSIONS: Laser resection of hyalin plaques in the vocal folds and skin is a feasible treatment for lipoid proteinosis. However, speech may remain severely limited, due to impaired tongue and lip movement.

[Lipoid proteinosis (Urbach-Wiethe's Disease)]. / Lipoid proteinozis (Urbach-Wiethe Hastaligi).

A 25-year-old female patient was admitted to our outpatient clinic with postpartum hoarseness. Punch biopsy specimens obtained from the larynx and sublingual region revealed multi-folded squamous epithelium with a hyperkeratosis pattern and amorphous hyaline material aggregation. This aggregation was also remarkable around the vessels. Histochemical examination showed periodic acid-schiff-positive staining of the basal membrane with negative staining with Congo red. Physical examination revealed papule-like itchy lesions in the whole body and hoarseness. Ophthalmological examination showed bilateral blepharitis. Tooth loss and yellowish papule formation in the oral mucosa were remarkable. The patient was diagnosed with lipoid proteinosis characterized by typical vocal cord involvement and conventional histopathological and clinical findings.

Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c.507delT mutation in ECM1.

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the ECM1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM1. LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging (MRI)/computed tomography (CT) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM1 were sought by PCR-based amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI/CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.

Should we think of Urbach-Wiethe disease in refractory epilepsy? Case report and review of the literature.

Urbach-Wiethe disease (UWD) is an autosomal recessive disease characterized by both neurological and dermatological manifestations. Face specially eyelids are commonly involved. Alopecia, nail dystrophy and dental anomalies have been reported as less frequent symptoms. Some patients show evidences of epilepsy and psychiatric symptoms such as schizophrenia, mood disorders, and anxiety due to calcium deposits in different parts of the brain. In this report, we describe the case of a young woman affected by UWD presenting with neurological involvements and no dermatological manifestations. This patient is a unique case of UWD as she has partial seizures and hoarseness. Also we summarize relevant data from the literature.

[Hyalinosis cutis et mucosae : 5 cases from Tabarka (Tunisia)]. / La hyalinose cutanéo-muqueuse : 5 cas originaires de Tabarka (Tunisie)

BACKGROUND: Hyalinosis cutis et mucosae (HCM), is a rare autosomal recessive genodermatosis. Cutaneous features are characteristic and allow to suspect diagnosis. AIM: To report a series of HCM. METHODS: A retrospective study of all cases of HCM, diagnosed in a dermatology department over a period of 25 years (1983-2007). RESULTS: Over the considered period, 5 new cases of HCM were diagnosed. Patients were aged between 14 and 41 years. They were 3 females and 2 males. All patients were native of Tabarka (northwestern Tunisia). The age of the onset of the disease varied from neonatal period to 5 years. Hoarseness was the first clinical manifestation in all cases. Skin lesions developed between the ages of 3 and 8 years. Vesiculobullous lesions were observed in 2 patients. Moniliform blepharosis was seen in all patients. Warty and hyperkeratotic papules were observed in 3 patients. Diffuse thickening of the skin was seen in 3 patients. Lesions were primarily distributed on the face. All patients presented diffuse scars. Linear palmoplantar keratoderma was seen in one patient. Asymptomatic endocranial calcifications were noted in 4 patients. A pituitary adenoma was noted in one patient. Histopathological examination of a skin lesion revealed a typical pattern of HCM. Two patients were treated with systemic retinoids without improvement. CONCLUSION: We reported five new cases of HCM. All patients were native from Tabarka. We report also one case of linear palmar keratoderma associated with HCM. This association was not reported in the literature. Finally, the association HCM-pituitary adenoma, seen in one patient, may be fortuitous.

Lipoid proteinosis of Urbach and Weithe: case report and a brief review of the literature.

Lipoid proteinosis is a rare disorder involving multiple organ systems. The ocular manifestations are usually trivial, but greatly aid in the diagnosis. We describe a patient who presented to us with typical moniliform blepharosis. A brief description of relevance to the ophthalmologist and review of the literature follows.