ABSTRACT
Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.Arg91Gln) in single-stranded DNA-binding protein 1 (SSBP1), a crucial protein involved in mtDNA replisome. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy. This mutation impeded multimer formation and DNA-binding affinity, leading to reduced efficiency of mtDNA replication, altered mitochondria dynamics, and compromised mitochondrial function. To correct this mutation, we tested two adenine base editor (ABE) variants on patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), showed higher editing efficacy (≤30%) and enhanced mitochondrial replication and function, despite off-target editing frequencies; however, risks from bystander editing were limited due to silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (≤10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. Taken together, base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated with SSBP1 mutations.
ABSTRACT
Sarcoidosis is a chronic multisystem granulomatous disease of unknown etiology. It is rare in young children. A 9-year-old boy presented with failure to thrive, skin rashes, persistent fever, and respiratory symptoms since 5 years of age. Blood investigations done showed elevated serum calcium and angiotensin converting enzyme levels and biopsy of the rashes on the left shin revealed non-caseating granulomatous lesion. Computed tomography of chest revealed interstitial lung disease and examination of eyes showed bilateral uveitis. He also had sensorineural hearing impairment, nephrocalcinosis, and short stature. The patient was treated with oral steroids and mycophenolate mofetil. At follow up, there was improvement in his systemic features including rashes and arthritis. Early detection, diagnosis, and appropriate treatment of sarcoidosis are vital for disease control and to avoid morbidity.
ABSTRACT
Background and Objectives: Wolfram syndrome type 1 (OMIM# 222300; ORPHAcode 3463) is an extremely rare autosomal recessive syndrome with a 25% recurrence risk in children. It is characterized by the presence of juvenile-onset diabetes mellitus (DM), progressive optic atrophy (OA), diabetes insipidus (DI), and sensorineural deafness (D), often referred to by the acronym DIDMOAD. It is a severe neurodegenerative disease with a life expectancy of 39 years, with death occurring due to cerebral atrophy. For a positive diagnosis, the presence of diabetes mellitus and optic nerve atrophy is sufficient. The disease occurs because of pathogenic variants in the WFS1 gene. The aim of this article is to present a case report of Wolfram Syndrome Type I, alongside a review of genetic variants, clinical manifestations, diagnosis, therapy, and long-term management. Emphasizing the importance of early diagnosis and a multidisciplinary approach, the study aims to enhance understanding and improve outcomes for patients with this complex syndrome. Materials and Methods: A case of a 28-year-old patient diagnosed with DM at the age of 6 and with progressive optic atrophy at 26 years old is presented. Molecular diagnosis revealed the presence of a heterozygous nonsense variant WFS1 c.1943G>A (p.Trp648*), and a heterozygous missense variant WFS1 c.1675G>C (p.Ala559Pro). Results: The molecular diagnosis of the patient confirmed the presence of a heterozygous nonsense variant and a heterozygous missense variant in the WFS1 gene, correlating with the clinical presentation of Wolfram syndrome type 1. Both allelic variants found in our patient have been previously described in other patients, whilst this combination has not been described before. Conclusions: This case report and review underscores the critical role of early recognition and diagnosis in Wolfram syndrome, facilitated by genetic testing. By identifying pathogenic variants in the WFS1 gene, genetic testing not only confirms diagnosis but also guides clinical management and informs genetic counseling for affected families. Timely intervention based on genetic insights can potentially reduce the progressive multisystem manifestations of the syndrome, thereby improving the quality of life and outcomes for patients.
Subject(s)
Early Diagnosis , Membrane Proteins , Wolfram Syndrome , Humans , Wolfram Syndrome/genetics , Wolfram Syndrome/diagnosis , Membrane Proteins/genetics , Adult , Male , Genetic Variation , Female , Optic Atrophy/genetics , Optic Atrophy/diagnosisABSTRACT
Wolff-Parkinson-White (WPW) syndrome is a condition associated with tachycardia due to accessory pathways in the heart, and it is one of the most common causes of tachycardia in infants and children. WPW may also be associated with mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS syndrome) or LEOPARD syndrome (LS). We report a case of pre-excitation WPW syndrome in a 17-year-old man who was brought to the hospital by ambulance following the collapse. WPW syndrome type A was diagnosed from precordial leads. Electrocardiography (ECG) revealed a short PR interval, delta waves, and positive waves with dominant R in all pericardial leads. Blood test results showed an isolated elevated ALT level. Subsequent echocardiography was unremarkable, with an ejection fraction of 55%, apart from septal and inferior wall dyssynchrony. With regard to the past medical history, he had sensorineural deafness (SND) since childhood and had a family history of SND. Consequently, the patient was transferred to the cardiac electrophysiology department at another hospital after consultation and underwent ablation. A successful post-ablation electrocardiogram revealed the resolution of the WPW syndrome signs and post-ablation features, such as peak T waves.
ABSTRACT
A heterozygous gain-of-function variant in the acyl-CoA oxidase 1 (ACOX1) gene, c.710A>G (p.Asn237Ser), is known to cause Mitchell syndrome, a very rare progressive disorder characterized by episodic demyelination, sensory polyneuropathy, and hearing loss. Only eight patients have been described so far. A single patient has been treated with intravenous immunoglobulin administration, indicating clinical improvement. In this study, we describe a 10-year-old girl carrying the identical mutation, who presented with progressive sensorineural deafness, visual abnormalities, skin ichthyosis, and gait ataxia from infantile age with progressive worsening and loss of walking ability by the age of 10 years. Antioxidant therapies and monthly intravenous immunoglobulin infusions showed excellent clinical results: after 1 year of treatment, the child is now able to walk, run, and jump. We emphasize the importance of early genetic diagnosis since an effective treatment is available for this rare condition.
ABSTRACT
Chudley-McCullough syndrome (CMS) is a rare autosomal recessive disorder characterized by sensorineural hearing loss and cerebral abnormalities, including ventriculomegaly and partial dysgenesis of the corpus callosum. CMS is caused by two inactivating mutations of the G protein signaling modulator 2 (GPSM2), which maintains inner hair cell polarity and spindle orientation. Since its initial description, CMS has been reported approximately 30 times in the medical literature with several individuals undergoing cochlear implantation to restore their hearing. Interestingly, within the past two years, we encountered two cases of CMS in our hospital, which primarily serves patients within a 30-mile radius. To our knowledge, the literature has yet to evaluate two unrelated cases of CMS occurring in such close succession. This case report describes two successful cases of bilateral cochlear implantation in two children with CMS. Notably, these individuals have no family history of consanguinity or prior hearing loss.
ABSTRACT
Johanson-Blizzard syndrome (JBS) is a rare hereditary autosomal recessive disorder caused by a mutation in the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene. This syndrome is characterized by the following typical clinical features: hypoplasia or aplasia of the alae nasi, congenital scalp defects, sensorineural hearing loss, hypothyroidism, growth retardation, psychomotor retardation, imperforate anus, genitourinary anomalies, and atypical hair patterns. Here, we describe a case of a 12-year-old girl with JBS of consanguineous parents. During the last trimester of pregnancy, a congenital abnormality affecting the nose was detected. Immediately after birth, the clinical examination revealed dysmorphic features in the form of hypoplastic alae nasi, microcephaly, mild hypotelorism, and cutis aplasia on the scalp. The genetic testing of the patient showed a novel sequence change mutation of the UBR1 gene (1bp duplication causing a frameshift), while both parents were carriers for this mutation. Moreover, a diagnosis of pancreatic insufficiency and subclinical hypothyroidism was made based on clinical presentation and laboratory results. The patient was started on pancreatic enzyme replacement therapy and fat-soluble vitamins, minerals, and antioxidant syrup. Further assessment revealed hypotonia, growth impairment, delay in reaching developmental milestones, and bilateral profound sensorineural hearing loss, which was managed with bilateral cochlear implantation. In addition, the patient underwent multiple craniofacial reconstructive surgeries. This case report highlights the importance of early diagnosis and multidisciplinary care of patients with JBS.
ABSTRACT
Spiral ganglion neurons (SGNs) transmit sound signals received by hair cells to the auditory center to produce hearing. The quantity and function are important for maintaining normal hearing function. Limited by the regenerative capacity, SGNs are unable to regenerate spontaneously after injury. Various neurotrophic factors play an important role in the regeneration process. Neuritin is a neurite growth factor that plays an important role in neural plasticity and nerve injury repair. In this study, we used bioinformatics analysis to show that neuritin was negatively correlated with cochlear damage. Then, we aimed to establish a cochlear spiral ganglion-specific sensorineural deafness model in gerbils using ouabain and determine the effects of exogenous neuritin protein in protecting damaged cochlear SGNs and repairing damaged auditory nerve function. The provides a new research strategy and scientific basis for the prevention and treatment of sensorineural deafness caused by the loss of SGNs. We were discovered that neuritin is expressed throughout the development of the gerbil cochlea, primarily in the SGNs and Corti regions. The expression of neuritin was negatively correlated with the sensorineural deafness induced by ouabain. In vitro and in vivo revealed that neuritin significantly maintained the number and arrangement of SGNs and nerve fibers in the damaged cochlea and effectively protected the high-frequency listening function of gerbils.
Subject(s)
Deafness , Hearing Loss, Sensorineural , Animals , Spiral Ganglion/metabolism , Gerbillinae , Ouabain/pharmacology , Cochlea , Neurons , Deafness/chemically induced , Deafness/metabolism , DenervationABSTRACT
BACKGROUND: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. CASES PRESENTATION: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. CONCLUSIONS: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.
Subject(s)
Anemia, Megaloblastic , Deafness , Diabetes Mellitus , Hearing Loss, Sensorineural , Humans , Child , Adult , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sensorineural/genetics , Thiamine/therapeutic use , Anemia, Megaloblastic/diagnosis , Anemia, Megaloblastic/drug therapy , Early Diagnosis , Deafness/complications , Deafness/drug therapyABSTRACT
We present a rare manifestation of a common pathology: left sided sensorineural hearing loss secondary to subclavian steal syndrome after thoracic endovascular aortic repair for complicated acute aortic dissection. We describe the vascular physiology that can result in unilateral hearing loss and provide a brief review of subclavian steal syndrome. This case report highlights the importance of avid clinical recognition of an atypical presentation of a common vascular disease.
ABSTRACT
We report two cases of Alport syndrome and compare the clinical presentations and imaging findings in these cases. The clinical examination consisted of best-corrected visual acuity (BCVA), direct ophthalmoscopy, and slit-lamp examination. Macular optical coherence tomography (OCT) and anterior segment OCT (AS-OCT) and were utilized to document the details of the anterior and posterior segment pathologies. In order to evaluate systemic presentations of Alport syndrome, nephrology, and otolaryngology were consulted for each patient. In this study, the first case was a 27-year-old female with progressive myopia, anterior lenticonus, and temporal retinal thinning found in the ocular examination that led to the diagnosis of Alport syndrome. She underwent clear lens extraction and intraocular lens implantation, restoring acceptable visual acuity. The second case was a 20-year-old male patient with low visual acuity, severe bilateral anterior lenticonus, bilateral cataract, and temporal retinal thinning. The patient later developed renal failure and is a candidate for kidney transplantation. In this case report, progressive renal failure, hearing loss, and ocular abnormalities were all observed. This is consistent with previously reported cases given the typical characteristics of Alport syndrome, a rare inherited disease. The severity of those characteristics was higher in the male subject, a finding also consistent with prior reports indicating that males are usually affected more frequently and more severely than females, given that Alport syndrome is generally inherited as an X-linked disorder. Additionally, anterior segment and macular OCTs seemed to be of considerable significance in the early diagnosis of Alport syndrome given the typical ocular manifestations e.g. anterior lenticonus or temporal retinal atrophy.
ABSTRACT
Superficial siderosis of the central nervous system (SSCNS) is a rare disease characterized by iron deposition on the tissue surface of the middle axis system. We report the case of a man in his late 40 s who was admitted to the hospital with ataxia. A physical examination revealed cerebellar ataxia, sensorineural deafness, and bilateral pyramidal tract injury. Susceptibility-weighted magnetic resonance imaging showed linear hypointense signals on the surface of the cerebral hemispheres, sulcus gyrus, lateral ventricles, and cerebellum. The patient underwent treatment with deferiprone, mecobalamin, and vitamin B1, and the symptoms were not aggravated. The patient's daily living ability was near normal after 1 year of follow-up. A literature review indicated that most SSCNS patients present diverse clinical manifestations. Clinicians may consider SSCNS in patients with hearing impairment and gait ataxia, especially for those receiving anticoagulant therapy and with a history of brain injury or accident.
Subject(s)
Brain Injuries , Hearing Loss, Sensorineural , Siderosis , Male , Humans , Siderosis/diagnosis , Siderosis/diagnostic imaging , Central Nervous System , Cell MembraneABSTRACT
Objective: Computed tomography (CT) images of the temporal bone of large vestibular aqueduct syndrome (LVAS) patients were used to establish 3D numerical models based on the structure of the inner ear, which are, in turn, used to construct inner ear fluid-solid coupling models. The physiological features and pathophysiology of LVAS were analyzed from a biomechanical perspective using finite element analysis. Methods: CT images of the temporal bone were collected from five children attending the Second Hospital of Dalian Medical University in 2022. The CT images were used to build 3D models of the inner ear containing the vestibular aqueduct (VA) by Mimics and Geomagic software, and round window membrane models and fluid-solid coupling models were built by ANSYS software to perform fluid-solid coupling analysis. Results: By applying different pressure loads, the deformation of the round window membranes occurred, and their trend was basically the same as that of the load. The deformation and stress of the round window membranes increased with the increase in load. Under the same load, the deformation and stress of the round window membranes increased with the expansion of the midpoint width of the VA. Conclusion: CT images of the temporal bone used clinically could establish a complete 3D numerical model of the inner ear containing VA. Fluctuations in cerebrospinal fluid pressure could affect inner ear pressure, and VA had a limiting effect on the pressure from cerebrospinal fluid. The larger the VA, the smaller the limiting effect on the pressure.
ABSTRACT
We present these two cases to emphasize the necessity of critical thinking and high suspicion of the disease (Rogers syndrome) to avoid potentially fatal situations due to its rarity and the importance of early treatment.
ABSTRACT
This report describes a case of cochlear implantation to treat profound deafness three months after a diagnosis of bacterial meningitis in a patient with a remote history of splenectomy. A 71-year-old woman with a remote history of a splenectomy over 20 years before presented with bilateral profound deafness that occurred as sequela from pneumococcal meningitis three months prior. The patient had been vaccinated against the 23-valent polysaccharide pneumococcal vaccine (PPV-23). The audiometric evaluation revealed no response in either ear. Imaging was suggestive of complete ossification of the right cochlea with partial ossification of the basal turn of the left cochlea. She underwent successful left-sided cochlear implantation. Standard post-implantation speech outcomes include consonant-nucleus-consonant (CNC) word and phoneme scores and Az-Bio in quiet and noise. The patient noted subjective improvement in her hearing. Performance measures markedly improved when compared to her pre-operative evaluation, which showed no aided sound detection. This case report highlights the possibility of meningitis many years after splenectomy that can result in profound deafness with labyrinthitis ossificans and the potential for hearing rehabilitation for cochlear implantation.
ABSTRACT
AIM: This European multicentric study aimed to prove safety and performance of the Bonebridge BCI 602 in children and adults suffering from either conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided sensorineural deafness (SSD). METHODS: 33 patients (13 adults and 10 children with either CHL or MHL and 10 patients with SSD) in three study groups were included. Patients were their own controls (single-subject repeated measures), comparing the unaided or pre-operative to the 3-month post-operative outcomes. Performance was evaluated by sound field thresholds (SF), word recognition scores (WRS) and/or speech reception thresholds in quiet (SRT) and in noise (SNR). Safety was demonstrated with a device-specific surgical questionnaire, adverse event reporting and stable pure-tone measurements. RESULTS: The Bonebridge BCI 602 significantly improved SF thresholds (+ 25.5 dB CHL/MHL/SSD), speech intelligibility in WRS (+ 68.0% CHL/MHL) and SRT in quiet (- 16.5 dB C/MHL) and in noise (- 3.51 dB SNR SSD). Air conduction (AC) and bone conduction (BC) thresholds remained stable over time. All adverse events were resolved, with none unanticipated. Mean audio processor wearing times in hours [h] per day for the CHL/MHL group were ~ 13 h for adults, ~ 11 h for paediatrics and ~ 6 h for the SSD group. The average surgical length was 57 min for the CHL/MHL group and 42 min for the SSD group. The versatility of the BCI 602 (reduced drilling depth and ability to bend the transition for optimal placement) allows for treatment of normal, pre-operated and malformed anatomies. All audiological endpoints were reached. CONCLUSIONS: The Bonebridge BCI 602 significantly improved hearing thresholds and speech understanding. Since implant placement follows the patient's anatomy instead of the shape of the device and the duration of surgery is shorter than with its predecessor, implantation is easier with the BCI 602. Performance and safety were proven for adults and children as well as for the CHL/MHL and SSD indications 3 months post-operatively.
Subject(s)
Brain-Computer Interfaces , Deafness , Hearing Aids , Hearing Loss, Mixed Conductive-Sensorineural , Hearing Loss, Sensorineural , Hearing Loss , Speech Perception , Adult , Humans , Child , Bone Conduction , Hearing , Hearing Loss, Mixed Conductive-Sensorineural/surgery , Hearing Loss, Conductive/surgery , Deafness/surgery , Hearing Loss/surgery , Hearing Loss, Sensorineural/surgery , Treatment Outcome , Multicenter Studies as TopicABSTRACT
Brucellosis is a zoonotic disease. It is also one of the neglected infectious diseases and is less well-known compared to other diseases. It is acquired from infected animals (cattle, sheep, goats, camels, pigs, or other animals) through the consumption of unpasteurized dairy products or contact with tissues or fluids. Sensory neural hearing loss (SNHL) in neurobrucellosis had been described in the literature, mostly as an incidental finding that otolaryngologists should consider in any patient with fever and a history of travel to the Middle East, Central or South America, or other brucellosis-endemic countries. We present a neurobrucellosis case with profound bilateral SNHL that was treated with combination antibiotic therapy for long periods of time and highlight the clinical course of the patient.
ABSTRACT
Introducción: La infección congénita por citomegalovirus es causa de pérdida auditiva y alteraciones cognitivas. La infección perinatal por este virus es más frecuente en neonatos< 1500 g y produce menos secuelas neurológicas. Objetivo: Describir la evaluación neurológica en el primer año de vida en niños muy bajo peso al nacer con infección por citomegalovirus. Métodos: Estudio descriptivo y longitudinal en el que se incuyeron 14 neonatos< 1500 g, con diagnóstico de infección congénita o perinatal por citomegalovirus; a los cuales se les realizó evaluación del neurodesarrollo, ultrasonido craneal, potenciales evocados auditivos de tallo cerebral y potenciales visuales a las 40 semanas, a los seis meses y al año de edad gestacional corregida. En la primera evaluación se realizó además, electroencefalograma. Resultados: El 43 por ciento tuvo infección congénita y 57 por ciento infección perinatal. A las 40 semanas se evaluaron completamente 79 % de los casos, a los seis meses 64 por ciento y al año 36 por ciento. No se observaron anormalidades en el ultrasonido craneal, ni en el electroencefalograma. Al año de edad corregida, se detectaron alteraciones ligeras del neurodesarrolo en 33,3 por ciento del total de casos (2/6) y con igual porcentaje en los niños con infección congénita (1/3) y perinatal (1/3). En ningún paciente evaluado se detectó sordera neurosensorial, ni daño del nervio visual. Conclusiones: Las alteraciones del neurodesarrollo encontradas al año de edad corregida pueden estar relacionadas con la prematuridad o la infección por citomegalovirus. El seguimiento a mediano y largo plazo es necesario para detectar otras secuelas neurológicas de debut tardío(AU)
Introduction: Congenital cytomegalovirus infection is a cause of hearing loss and cognitive impairments. Perinatal infection by this virus is more frequent in neonates< 1500 g and produces fewer neurological sequelae. Objective: To describe neurological evaluation in the first year of life in very low birth weight children with cytomegalovirus infection. Methods: A descriptive and longitudinal study involving 14 neonates< 1500 g, with a diagnosis of congenital or perinatal cytomegalovirus infection; to which neurodevelopmental evaluation, cranial ultrasound, auditory brain stem evoked potentials and visual potentials were performed at 40 weeks, six months and one year of corrected gestational age. In the first evaluation, electroencephalogram was also performed. Results: 43 percent had congenital infection and 57 percent perinatal infection. At 40 weeks, 79 percent of cases were fully evaluated, at six months 64 percent and at one year 36 percent. No abnormalities were observed on the cranial ultrasound or electroencephalogram. At one year of corrected age, slight alterations in neurodevelopment were detected in 33.3 percent of all cases (2/6) and with the same percentage in children with congenital (1/3) and perinatal (1/3) infection. In no patient evaluated, sensorineural deafness or visual nerve damage was detected. Conclusions: The neurodevelopmental alterations found at one year of corrected age may be related to prematurity or cytomegalovirus infection. Medium- and long-term follow-up is necessary to detect other late-onset neurological sequelae(AU)
Subject(s)
Humans , Infant, Newborn , Aftercare/methods , Cytomegalovirus Infections/etiology , Infant, Very Low Birth Weight/growth & development , Hearing Loss, Sensorineural , Epidemiology, Descriptive , Longitudinal Studies , Cytomegalovirus/genetics , Observational Studies as TopicABSTRACT
Alström syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition. Here we report on a 12 year old boy referred to the University Clinic with early signs of impaired hearing and vision, obesity, and scoliosis. Central vision was first affected, followed by peripheral vision. In addition, his weight began increasing after the age of two years, reaching 78 kg at a height of 157 cm (BMI 31.64). No polydactyly was present. His mental development was normal in spite of his hearing and vision impairments. There was acanthosis nigricans on the neck. ECG and the cardiac ultrasound were normal. At the age of 12 years, his testicles are 12 ml and his pubertal status is P2 A2. OGTT revealed impaired glucose tolerance with elevated insulin concentrations 121ulU/mL (reference range 2,00-29,1 ulU/mL). Renal function was unaffected, liver functions were normal. Uric acid and lipids were within normal plasma concentrations. A Whole Exome Sequencing was performed and a homozygous ALMS1 pathogenic, frameshift gene variant (LRG_741t1(ALMS1):c.4156dup; p.Thr1386AsnfsTer15) was determined as the cause of the disease. Both parents were carriers for the variant. The absence of mental retardation and polydactyly differentiates Alström and Bardet-Biedle syndrome.