Nail-patella Syndrome Research Articles

The role of persistent right umbilical vein in the diagnosis of fetal genetic syndromes.

Persistent right umbilical vein (PRUV) is an embryonic vascular abnormality. Recent studies suggested that the perinatal outcome was good and the risk of aneuploidy was low in isolated forms. Our purpose in this study was to assess the relation of PRUV with genetic abnormalities and demonstrate concomitant malformations and perinatal outcomes of these fetuses. This was a retrospective study examining consecutive pregnancies diagnosed as having PRUV in our hospital between 2017 and 2022. A total of 41 patients were diagnosed as having fetuses with PRUV during the study period. Additional ultrasound findings were detected in 26 fetuses (63.4%). The most common associated finding was fetal growth restriction, which was found in 15 (36.5%) of 41 fetuses. This was followed by cardiovascular findings in eight (19.5%) fetuses. Genetic anomalies were detected in five (12.1%) fetuses. Down syndrome was detected in two fetuses (4.8%), nail-patella syndrome in one fetus (2.4%), duplication of 7p was found in one fetus (2.4%), and Potocki-Lupski syndrome (2.4%) was diagnosed in one fetus. In our study we found that even in isolated cases, genetic syndromes could coexist and fetal growth could be impaired so it should be closely monitored.

Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain. Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD. The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44–0.86], p < 0.0001). Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.

Nail-Patella Syndrome Presenting with Nephrotic Syndrome during Pregnancy

Nail-Patella Syndrome Presenting with Nephrotic Syndrome during Pregnancy

Nail Patellar Syndrome (NPS)

The Nail Patellar Syndrome (NPS) is a genetic disorder primarily involving the bones, nails and kidneys. Inheritance is autosomal dominant with unknown pathogenesis. Diagnostic features are hypoplastic or absent nails, patella, iliac horns and elbow abnormalities. Multiple other bony deformities, eye strucure abnormalities and nephropathy are seen. A case of 3-year old female child with nail patellar syndrome is presented.

Orthodontic and Surgical Management of Meir-Gorlin Syndrome: 7 Years of Follow-Up

Introduction: Meier-Gorlin syndrome (MGS) has three characteristics: short stature, a small or absent patella, and microtia. Objective: This case report aimed to evaluate orthodontic surgical treatment in a patient with MGS during a 7-year follow-up. Methods: A multidisciplinary approach was performed involving orthodontics and maxillofacial surgery. In the initial phase, orthodontic procedures were performed using rapid expansion of the mid-palatal suture. Orthodontic appliances (Roth prescription) were used and orthodontic decompensation was performed, followed by orthodontic surgery to make aesthetic and functional changes. Results: Surgical orthodontic treatment reduced proclination and protrusion and improved overbite. An adequate correlation of the upper and lower arches was achieved. Aesthetic and functional changes were observed, as well as the opening of the airways. Conclusion: This case report highlights the importance of orthodontic surgical correction to achieve symmetry and functionality, given the facial and physical characteristics present in this syndrome.

Clinical and radiological variants of the nail–patella syndrome: Why is it important to make a correct diagnosis?

BACKGROUND: Nail–patella syndrome is an autosomal dominant disease caused by LMX1B mutations, characterized by a combination of dermatological and musculoskeletal abnormalities. The classic tetrad of the nail–patella syndrome includes hypoplasia of the nail plates, absence or hypoplasia of the patella, elbow joint contractures, often accompanied by posterior subluxation of the radial head, presence of “iliac horns” on radiographs of the pelvic bones, and renal changes. However, its diagnosis and treatment are not described in sufficient detail in domestic and foreign literature. AIM: This study aimed to analyze the variability of clinical and radiological manifestations in children with nail–patella syndrome. MATERIALS AND METHODS: Nine patients with nail–patella syndrome were examined and treated (aged 4 months to 14 years). All children presented to the H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery with a diagnosis of congenital multiple arthrogryposis. The examination results excluded this diagnosis. The diagnosis of nail–patella syndrome has been verified. RESULTS: Various variants of the nail–patella syndrome have been identified, with lesions to only the elbow joints (n = 3), damage to the upper and lower extremities (n = 5), and damage to only the lower extremities (n = 1). All patients had hypoplasia of fingernail plates. However, the pathognomonic sign – “iliac horns” on radiographs of the pelvic bones – was noted only in 33% of cases. Regarding functional disorders of the kidneys, proteinuria was observed in one patient, which appeared at the age of 15 years. In two cases, the parents suffered from this disease. A genetic examination was performed in three patients: a pathogenic variant in LMX1B was detected in a heterozygous state. All patients underwent conservative treatment for knee and elbow joint contractures and foot deformities. When casting, the presence of dislocation of the radial head or patella was considered. Surgical treatment was performed on five patients. The results of surgery on the lower extremities (knee contractures, foot deformities, and hip dislocation) were good in 87% of the cases. Recurrence of flexion contractures in the elbow joints was observed both after conservative and after surgical treatment in all cases; however, their severity varied. CONCLUSIONS: Clinical observations were considered to attract the attention of doctors of different specialties to a rare pathology. Moreover, a molecular genetic study is recommended for the timely diagnosis of the nail–patella syndrome, determining the treatment techniques and disease prognosis.

Exome sequencing of 1190 non-syndromic clubfoot cases reveals HOXD12 as a novel disease gene

BackgroundClubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants...

#3084 Familial nephropathy associated with a combined mutations of Alport and Nail Patella syndrome genes in the same family

Abstract Introduction Alport syndrome is a genetic condition stemming from mutation in Type IV collagen and is characterized by kidney disease and frequently hearing loss and ocular abnormalities. Renal involvement is from an abnormality of the glomerular basement membrane with hematuria and proteinuria progressing eventually to renal failure. In the vast majority, the inheritance is X- linked affecting the alpha 5 chain of type IV collagen while in about 15 percent of the patients the inheritance is autosomal recessive or dominant with mutations affecting alpha 3 or 4 chains of type IV collagen. Sensorineural deafness is common and ocular abnormalities may include lenticonus, corneal opacities, fleck retinopathy and temporal retinal thinning. Nail Patella syndrome (NPS) is a rare genetic condition from mutation in the LMX1B gene on chromosome 9 with an autosomal dominant inheritance. Glomerular disease is from characteristic glomerular basement membrane changes and is associated with nail, pelvic girdle and limb abnormalities. A forme fruste with glomerular lesions but lacking extrarenal features is recognized but uncommon. We present a family with mutations in both COL4A5 and LMX1B presenting with hematuria and proteinuria Case Presentation A 23 year old female was evaluated for hematuria and proteinuria. Her history was notable for kidney biopsy at the age thirteen showing focal and segmental glomerulosclerosis (FSGS). She was treated with tacrolimus for four years from age thirteen through seventeen. Patient was reportedly diagnosed with Nail Patella Syndrome after genetic testing. Her family history was notable for hematuria in her brother and hematuria and proteinuria in her mother. On physical examination she was noted to have no nail or skeletal abnormalities associated with Nail Patella Syndrome. Her labs were notable for a serum creatinine of 0.6 mg/dl and proteinuria of 155 mg/g creatinine of proteinuria. Urine microscopy revealed dysmorphic hematuria. Radiological imaging did not show skeletal abnormalities observed in Nail Patella Syndrome but genetic testing identified a pathogenic variant in COL4A5 c.919G&amp;gt;A (p.Gly307Ser) in addition to a variant of uncertain significance in LMX1B c.349G&amp;gt;A (p.Gly117Ser). Her brother aged 20 had a creatinine of 0.87 mg/dl with dysmorphic hematuria and no proteinuria. Genetic testing showed the same pathogenic variant in COL4A5 as in his sibling. His mother aged 55 was subsequently evaluated and had a creatinine 0.73 mg/dl with dysmorphic hematuria and 152 mg/g of proteinuria. Genetic testing was with the same variant in COL4A5 noted in her two children. Renal biopsy was extensive thinning and segmental lamellation of the glomerular basement membrane with eight percent FSGS. The typical “moth-eaten” appearance of the glomerular basement membrane characteristic of NPS was not evident. Segmental staining was observed with alpha 5 unit of Type IV collagen. Audiology and retinal optical coherence optometry studies are pending. Discussion Alport syndrome and Nail Patella Syndrome are rare genetic disorders that cause variable degrees of renal insufficiency from glomerular base membrane defects and are associated with characteristic extra renal manifestations. This is the first report of an inherited nephritis with combined mutations in COL4A5 and LMX1B. The clinical features and renal biopsy are compatible with Alport Syndrome and the significance of the mutation in LMX1B is uncertain. Conclusion This is the first case report of a combined mutation in COL4A5 and LMX1B gene presenting with hematuria and minimal proteinuria with preserved kidney function.

A Modified 4-in-1 Stanisavljevic Procedure for Treating Obligatory or Congenital Patellar Dislocations in Children: A Surgical Technique.

Patellar instability and dislocation pose complex clinical and surgical challenges, especially in children. Congenital (fixed) and obligatory (habitual) dislocations present significant anatomical and etiological complexity, frequently leading to deformities and functional impairments, which can range from walking difficulties to sports limitations. Conservative treatment is often inadequate. We describe a surgical technique for treating congenital or obligatory patellar dislocations in patients with various underlying diagnoses-including Down syndrome, nail-patella syndrome, and skeletal dysplasia-that involves extensive subperiosteal quadriceps realignment, distal realignment (Roux-Goldthwait or tibial tuberosity transfer), and optional medial plication. This modified 4-in-1 technique follows the principles described in 1976 by Stanisavljevic, which involves subperiosteal quadriceps mobilization, thus minimizing muscle damage, bleeding, and postoperative muscular adherences. In 24 patients treated at our institution between 2002 and 2021 (35 knees; age range = 5.5-16.8 years; 13 girls, 11 boys), with a mean follow-up of 8.2 years (2.4-20 years), we achieved satisfactory improvements in patellar stability, range of motion, and quality of life with a modified 4-in-1 Stanisavljevic technique. A total of 9 patients (7 with obligatory dislocations and 2 with congenital dislocations) could engage in recreational or competitive sports. The average postoperative pediatric International Knee Documentation Committee (pedi-IKDC) score was 78.45 ± 22.3 (range = 0-100); a patient with DiGeorge syndrome and 1 with multiple epiphyseal dysplasia had scores of 35 and 48, respectively. We found at our institution that a modified 4-in-1 Stanisavljevic technique produced favorable outcomes in patellar stability, range of motion, and quality of life in pediatric patients with congenital or obligatory patellar dislocation. More study is warranted to determine the procedure's overall benefits for children with obligatory or congenital dislocations of complex etiology.

A deletion variant in LMX1B causing nail–patella syndrome in Japanese twins

Nail–patella syndrome (NPS) is a hereditary disease caused by pathogenic variants in LMX1B and characterized by nail, limb, and renal symptoms. This study revealed a likely pathogenic LMX1B variant, NM_002316.4: c.723_726delinsC (p.Ser242del), in Japanese twins with clubfoot. The patients’ mother, who shared this variant, developed proteinuria after delivery. p.Ser242del is located in the homeodomain of the protein, in which variants that cause renal disease tend to cluster. Our findings highlight p.Ser242del as a likely pathogenic variant, expanding our knowledge of NPS.

The first presentation of a case of nail-patella syndrome newly diagnosed at the onset of rheumatoid arthritis: a case report

/SummaryBackgroundNail-patella syndrome (NPS) is a rare autosomal dominant disorder that is characterized by dysplasia of the nails, hypoplasia and/or dislocation of the patella and the presence of iliac horns. Using the CARE guidelines, we present the first reported case of NPS that was newly diagnosed at the onset of rheumatoid arthritis (RA).Case presentationA 74-year-old man was admitted to our hospital due to an 8-month history of arthralgia in bilateral wrists, elbows and fingers. He had a past history of glaucoma and left patella dislocation that had been operatively recentered at the age of 15 years. Laboratory data showed elevated levels of serum C-reactive protein and rheumatoid factor and an elevated titer of anti-SS-A antibodies, while estimated glomerular filtration rate (eGFR), titers of other antibodies and the results of a urinary test were normal. An X-ray showed deformity of bilateral radial heads and the right elbow, and magnetic resonance imaging (MRI) of his hands showed synovitis and erosion in the multiple swollen joints of the wrists and fingers. In addition to these typical features of RA, he had bilateral thumb nail dysplasia with mild hypoplasia of bilateral patellae and iliac horns as shown by the X-ray. He was diagnosed as having autosomal dominant disorder NPS co-existing with RA and he was treated with methotrexate in combination with an oral Janus kinase (JAK) inhibitor, leading to induction of remission.ConclusionsWe have presented a rare case of NPS that was newly diagnosed at the onset of RA. Clinical and radiographic findings of NPS are highlighted in this case report for diagnosing NPS on the basis of typical manifestations.

The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration.

The limb anatomy displays well-defined dorsal and ventral compartments, housing extensor, and flexor muscles, which play a crucial role in facilitating limb locomotion and manipulation. Despite its importance, the study of limb dorsoventral patterning has been relatively neglected compared to the other two axes leaving many crucial questions about the genes and developmental processes implicated unanswered. This review offers a thorough overview of the current understanding of limb dorsoventral patterning, synthesizing classical literature with recent research. It covers the specification of dorsal fate in the limb mesoderm and its subsequent translation into dorsal morphologies-a process directed by the transcription factor Lmx1b. We also discuss the potential role of dorsoventral patterning in the evolution of paired appendages and delve into the involvement of LMX1B in Nail-Patella syndrome, discussing the molecular and genetic aspects underlying this condition. Finally, the potential role of dorsoventral polarity in digit tip regeneration, a prominent instance of multi-tissue regeneration in mammals is also considered. We anticipate that this review will renew interest in a process that is critical to limb function and evolutionary adaptations but has nonetheless been overlooked.

Anesthetic Challenges and Goals in a 17-Year-Old Patient with Nail Patella Syndrome Undergoing Emergency Open Appendectomy: A Case Report

This case report delves into the intricate anesthetic management of a 17-year-old male presenting Nail Patella Syndrome (NPS) and end-stage renal failure necessitating emergency open appendectomy. NPS, an uncommon hereditary disorder, manifests with distinct abnormalities affecting the nails, patellae, elbows, and iliac crests, thereby complicating perioperative care. The patient's extensive medical history, notably including hypertension and chronic renal disease, posed formidable challenges during anesthesia administration. Addressing these complexities required a meticulous approach, tailoring anesthetic goals to mitigate risks while striving for optimal outcomes. Despite the inherent intricacies associated with NPS, successful perioperative management was realized through careful planning and execution of anesthesia protocols. This case underscores the critical role of individualized care and interdisciplinary collaboration in navigating the multifaceted challenges posed by rare genetic conditions, especially in emergency surgical scenarios. By shedding light on the nuanced considerations and strategies employed in this instance, this report contributes valuable insights to the broader discourse surrounding the management of NPS patients undergoing surgical interventions, enriching our understanding of effective approaches in emergency settings.

Nail Patella Elbow Syndrome Presenting with Depression: A Case Report

Nail-Patella Syndrome (NPS) is a rare autosomal dominant illness. Patients typically exhibit a tetrad of dysplastic finger or toenails, elbow dysplasia, hypoplastic or missing patellae, and iliac horns as their first musculoskeletal and dermatological symptoms. A higher occurrence of psychiatric disorders, such as depression and attention deficit hyperactivity disorder, has also been reported with NPS. This is a rare case of NPS, presenting with depression as the major symptom in an 18-year-old young girl who presented to the psychiatry Outpatient Department (OPD) with depressive symptoms like persistent low mood, loss of pleasure or anhedonia, loss of appetite, disturbed sleep, and thoughts of death. After 10 days of treatment with antidepressant drugs like Benzodiazepines, she was discharged and followed-up on an OPD basis. After a thorough evaluation, hypoplastic patella, swan-necked nails, radial head subluxation, and right eye glaucoma were also noted, and a final diagnosis of Nail-Patella Syndrome was made. A case of NPS can present in any department, such as in Medicine for nail dysplasia, in Orthopaedics for elbow or patella dysplasia, or in Dermatology for iliac horns. Here, the case was primarily presented to the Psychiatry department and later managed by a team of physicians, orthopaedicians, and psychiatrists. Careful illustration of the family history reveals more cases.

De novo enhancer deletion of LMX1B produces a mild nail-patella clinical phenotype.

Critical genes involved in embryonic development are often transcription factors, regulating many downstream genes. LMX1B is a homeobox gene that is involved in formation of the limbs, eyes and kidneys, heterozygous loss-of-function sequence variants and deletions cause Nail-Patella syndrome. Most of the reported variants are localised within the gene's coding sequence, however, approximately 5%-10% of affected individuals do not have a pathogenic variant identified within this region. In this study, we present a family with four affected individuals across two generations with a deletion spanning a conserved upstream LMX1B-binding sequence. This deletion is de novo in the mother of three affected children. Furthermore, in this family, the manifestations appear limited to the nails and limbs, and therefore may reflect an attenuated phenotype of the classic Nail-Patella phenotype that includes ophthalmological and renal manifestations.

Nail–patella syndrome

Nail–patella syndrome

Chronic Knee Pain is the Paramount Presentation in Patients with Nail-Patella Syndrome

Background: Arthralgia in connection with patellar instability have been studied thoroughly in a number of pediatric and adult patients. Small and dysplastic patellae accompanied by hypoplasia of the lateral femoral condyle may results in recurrent subluxation or dislocation of the patellae, knee discomfort and pain. We aimed to detect the underlying etiology of every single patient. Patients and Methods: A total of seven children presented with long term painful knee joints have been refered from the departments of rheumatology. We added adult female patient of a-35-years-old. She was a chronic client of rheumatology clinics since her postadulthood. In addition to her early life knee pain. Recently she experienced additional chronic pain of the groin (located at the posterior buttocks). All our patients showed episodes of knee pain with variable intensity as a constant complaint and all received antirheumatic treatments for years despite the negative results of the implemented tests. In order to commence the diagnostic process, clinical and radiological phenotypic characterization were the main core of our stratregy followed by molecular genetic confirmation. Results: Seven unrelated children (aged from 8-17 years old) were consistent with the diagnosis of Nail- Patella syndrome. The adult female patient of a-35-years-old- manifested patellar instability since her early childhood. Her clinical phenotype was totally compatible with the diagnosis of Nail-Patella syndrome. Surprisingly, the clinical examination of the female patient and the standing AP pelvis radiograph revealed massive encroachment of the medial aspect of the femoral neck and the lesser trochanters onto the ischium. The latter resulted in the diagnosis of Ischiofemoral Impingement (IFI) syndrome. Her genetic tests showed heterozygous mutation in the LIM-homeodomain protein LMX1B on chromosome 9q33. Conclusion: Arthralgia associated with abnormal gait (mostly antalgic gait and waddling gait) was the paramount clinical presentation in all our patients. Dysplasia of the nails and patellar instability were the characteristic clinical findings in our patients with the definite diagnosis of osteo-onychodysplasia syndrome. We approached to the diagnosis from the first session of clinical examination. Interestingly, the constant groin pain in the adult female patient which has been totally overlooked by other instutions, were in favor of the diagnosis of Ischiofemoral Impingement (IFI) syndrome. As well as the existing abnormality of the elbows associated with defective pronation and supination as due to impingement of the olecranon. The task of establishing the diagnostic process in complex clinical conditions is the most challenging. Sadly speaking, none of the aforemnetioned dignostic criteria attracted the attention of dozens of clinicians. Admistering medications to overcome knee pain through dozens of useless laboratory tests were the main false issue. Clinicians who are actively involved in clinical diagnosis with minimal dependency on laboratory aid are generally at the forefront of their medical fields.

Chronic Knee Pain is the Paramount Presentation in Patients with Nail-Patella Syndrome

Background: Arthralgia in connection with patellar instability have been studied thoroughly in a number of pediatric and adult patients. Small and dysplastic patellae accompanied by hypoplasia of the lateral femoral condyle may results in recurrent subluxation or dislocation of the patellae, knee discomfort and pain. We aimed to detect the underlying etiology of every single patient. Patients and Methods: A total of seven children presented with long term painful knee joints have been refered from the departments of rheumatology. We added adult female patient of a-35-years-old. She was a chronic client of rheumatology clinics since her postadulthood. In addition to her early life knee pain. Recently she experienced additional chronic pain of the groin (located at the posterior buttocks). All our patients showed episodes of knee pain with variable intensity as a constant complaint and all received antirheumatic treatments for years despite the negative results of the implemented tests. In order to commence the diagnostic process, clinical and radiological phenotypic characterization were the main core of our stratregy followed by molecular genetic confirmation. Results: Seven unrelated children (aged from 8-17 years old) were consistent with the diagnosis of Nail- Patella syndrome. The adult female patient of a-35-years-old- manifested patellar instability since her early childhood. Her clinical phenotype was totally compatible with the diagnosis of Nail-Patella syndrome. Surprisingly, the clinical examination of the female patient and the standing AP pelvis radiograph revealed massive encroachment of the medial aspect of the femoral neck and the lesser trochanters onto the ischium. The latter resulted in the diagnosis of Ischiofemoral Impingement (IFI) syndrome. Her genetic tests showed heterozygous mutation in the LIM-homeodomain protein LMX1B on chromosome 9q33. Conclusion: Arthralgia associated with abnormal gait (mostly antalgic gait and waddling gait) was the paramount clinical presentation in all our patients. Dysplasia of the nails and patellar instability were the characteristic clinical findings in our patients with the definite diagnosis of osteo-onychodysplasia syndrome. We approached to the diagnosis from the first session of clinical examination. Interestingly, the constant groin pain in the adult female patient which has been totally overlooked by other instutions, were in favor of the diagnosis of Ischiofemoral Impingement (IFI) syndrome. As well as the existing abnormality of the elbows associated with defective pronation and supination as due to impingement of the olecranon. The task of establishing the diagnostic process in complex clinical conditions is the most challenging. Sadly speaking, none of the aforemnetioned dignostic criteria attracted the attention of dozens of clinicians. Admistering medications to overcome knee pain through dozens of useless laboratory tests were the main false issue. Clinicians who are actively involved in clinical diagnosis with minimal dependency on laboratory aid are generally at the forefront of their medical fields.

Nail-patella syndrome.

Nail-patella syndrome is a rare disorder with \&amp;apos;\&amp;apos; iliac horns\&amp;apos;\&amp;apos; its pathognomonic sign in X-ray pelvis. May I submit this case image for educational purposes of all colleagues and trainees?

Unusual genotypic and phenotypic presentation in a patient with nail‐patella syndrome

AbstractPurpose: Nail‐Patella syndrome (NPS) is an autosomal dominant hereditary disease. It is characterized by a mutation in the gene that codes for the transcription factor LMX1B located on chromosome 9q34, essential for proper development of the musculoskeletal, renal, nervous and ocular systems. At the ophthalmological level, alterations of the anterior segment, ocular hypertension and its possible progression to glaucoma stand out.Methods: 21‐year‐old male who presents from birth short stature, reduced muscle mass, hypoplastic patella, involvement of fingernails and toenails, and progressive kidney failure. His genetic study shows an homozygous mutation in the LMX1B gene with c.376G &gt; A (p.Glu126Lys) variant. Ophthalmologically, there are no symptoms. On examination, visual acuity is 0.9 in both eyes. Biomicroscopy shows a wide anterior chamber, bilateral gerontoxon and the presence of frayed iris. Gonioscopy shows an open angle without alterations in its structures. The intraocular pressure (IOP) measured by Goldmann tonometer is 3 mmHg in the right eye and 4 mmHg in the left eye, which is maintained in subsequent visits. The ocular fundus reveals a physiological papilla in both eyes and no signs of glaucomatous involvement. The visual field, macular, papillary and anterior segment optical coherence tomography are compatible with normality.Conclusions: the patient presents a typical NPS but with ocular hypotension that is not clinically significant and the mutation is homozygous. The usual ocular alterations occur in the drainage structures of the aqueous humour that cause an increase in IOP to a variable degree. Although ciliary body hypoplasia with atrophy of the ciliary processes has been described in animal models, which would produce an absence or decrease in the production of aqueous humour, no human case with ocular hypotony has been described in the current literature.