Prenatal diagnosis and pedigree analysis of a case of Nail-patella syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carried out prenatal diagnosis and genetic analysis for a case with Nail-patella syndrome.@*METHODS@#Based on the clinical phenotype and prenatal imaging, genetic testing and prenatal diagnosis were carried out through whole exome sequencing (WES) and Sanger sequencing.@*RESULTS@#Analysis of amniotic fluid showed that the fetus has carried a heterozygous c.139+1G>T splicing site variant [Chr9(GRCh37): g.129376868G>T] of the LMX1B gene, which was verified by Sanger sequencing. The same heterozygous variant was found in the pregnant woman, her daughter and her mother but not in her husband. Searching of HGMD database showed that the c.139+1G>T was previously unreported.@*CONCLUSION@#Nail-patella syndrome is an autosomal dominant genetic disorder with various clinical manifestations. WES is helpful for its genetic and prenatal diagnosis.

Paciente con asociación de síndrome uña-rótula y artrogriposis múltiple congénita. Evolución clínico-radiológica / Patient with association of nail-patella syndrome and multiple congenital arthrogryposis. Clinical radiological evolution

RESUMEN La asociación de la artrogriposis múltiple congénita con el síndrome uña -rótula es rara, porque ambas patologías son infrecuentes. Debido a la gran variedad de manifestaciones clínico-radiológica de ambos síndromes, es necesario conocer el cuadro clínico de cada una de ellas para poder identificar el origen de todas las afectaciones encontradas en el paciente, una vez alcanzada la adultez. Se presentó un paciente adulto tratado durante su infancia en el Hospital Pediátrico “Eliseo Noel Caamaño”, de Matanzas, con la asociación de ambas entidades, con el fin de observar su estado anatómico, funcional y radiológico actual. El objetivo fue estudiar la evolución clínico-radiológica del paciente a través del tiempo. Se concluyó que en este tipo de patologías se producen severas deformidades del Sistema Osteomioarticular, así como de otros sistemas, por lo que se requiere de un trabajo multidisciplinario y de un estricto seguimiento para lograr personas útiles a la sociedad a pesar de sus limitaciones físicas... (AU)

ABSTRACT The association of multiple congenital arthrogryposis with nail-patella syndrome is rare, because both pathologies are infrequent. Due to the great range of clinical radiological manifestations of both syndromes, it is necessary to know the clinical characteristics of each of them to identify the origin of these affections found in the patient after reaching the adulthood. It is presented an adult patient treated during the childhood in the Pediatric Hospital ¨Eliseo Noel Caamaño¨, of Matanzas, with the association of both entities, to observe his current anatomic, functional and radiological status. The aim was studying the patient´s clinical radiological evolution through the time. The conclusion we arrived at was that this kind of pathologies produce severe deformities of the Osteomyoarticular System and also of other systems, so it is required a multidisciplinary approach and a strict follow-up to offer the society useful persons in spite of their physical limitations...(AU)

Talla baja e hipotiroidismo en un niño con Síndrome de Nail-Patella. Reporte de un caso clínico / Short stature and hypothyroidism in a child with Nail-Patella Syndrome. A case report

Resumen: Introducción: El síndrome de Nail-Patella (NPS) es un desorden autosómico dominante caracterizado por anomalías esqueléticas, displasia ungueal, alteraciones renales y oculares. El diagnóstico se sospecha con la clínica y radiología y se confirma por la identificación de una variante patogénica en el gen LMX1B. El manejo de estos pacientes implica un seguimiento continuo y el tratamiento de las posibles complicaciones ortopédicas, oculares y renales. Objetivo: Describir un caso de NPS con talla baja e hipotiroidismo, asociación que no ha sido descrita en la literatura. Caso clínico: Adolescente de 11 años con talla 130 cm (-2,01 Desviaciones Estándar [DE]) fue referido a Endocrinología a los 2 años de edad por pruebas tiroideas alteradas. Se detectaron uñas displásicas y talla baja despro porcionada, además de anormalidades radiológicas sugerentes de displasia esquelética. Se confirmó hipotiroidismo primario, con anticuerpos negativos y ecografía normal, por lo que se inició trata miento con levotiroxina. El diagnóstico de NPS fue confirmado mediante estudio genético de ADN constatándose una variante patogénica en el gen LMX1B. Su padre presentaba un fenotipo similar, con estatura normal. Su edad ósea era acorde con la cronológica. Tanto el estudio general de talla baja como un test de clonidina para estimulación de GH fueron normales. Conclusión: Presentamos un paciente con NPS confirmado, asociado a talla baja e hipotiroidismo. No hallamos publicaciones en la literatura que describieran esta triple asociación. No se descarta que podría haber una relación entre el NPS y las alteraciones tiroideas halladas en este paciente.

Abstract: Background: Nail-Patella syndrome (NPS) (OMIM: 161200) or hereditary onycho-osteodysplasia is an autosomal dominant disorder characterized by skeletal anomalies, nail dysplasia, renal and ocular abnor malities. The diagnosis is based on clinical and radiological findings and confirmed by the identification of a heterozygous pathogenic variant in the LMX1B gene. Management of these patients involves conti nuous follow-up and treatment ofthe orthopedical, ocular and renal problems that mayoccur. Objective: To describe a case of NPS with short stature and hypothyroidism, an association that has not been described in the literature. Case report: An eleven-year-old boy with a height of 130 cm (-2.01 Stan dard Deviations [SD]) was referred to the Endocrine Unit at the age of 2 years due to altered thyroid tests. At that time, dysplastic nails and disproportionate short stature were detected. Radiological abnormalities initially suggested a skeletal dysplasia. A primary hypothyroidism was confirmed, without anti-thyroid antibodies and with a normal thyroid ultrasound. Levothyroxine treatment was initiated. The diagnosis of NPS was confirmed by a genetic study with a single pathogenic variant in the LMX1B gene. His father presented a similar phenotype with normal stature. His bone age was equivalent to his chronological age. Laboratory screening for short stature and a GH stimulation test were normal. Conclusion: We present a child with proven NPS with short stature and hypothyroi dism. We did not find publications that described this triple association. It can't be ruled out that there could be a relationship between NPS and the thyroid alterations found in this patient.

A Case of Congenital Glaucoma in Associated with Nail-patella Syndrome

PURPOSE: To report a case of congenital glaucoma associated with nail-patella syndrome. CASE SUMMARY: A 20-day-old female was referred to our clinic for bilateral intraocular pressure (IOP) elevation and treatment of corneal opacities. Her IOP was 25 mmHg and 30 mmHg in the right and left eyes, respectively. After a diagnosis of congenital glaucoma, bilateral trabeculotomy was performed under general anesthesia. On the first postoperative day, the IOP was 12 mmHg in the right eye and 10 mmHg in the left eye, and remained stable thereafter. The infant was the second of fraternal twins (birth weight of 2.42 kg) and had no family history of any particular disease. During the regular checkup, she was referred to an orthopedic clinic for disorders of the elbow and knee. She presented with a dystrophic thumbnail, patella hypoplasia, elbow hypoplasia, and bilateral triangular protrusions of the lateral iliac crest (iliac horn). Based on the above findings, typical nail-patella syndrome was diagnosed and a mutation in the LMX1B gene was detected. CONCLUSIONS: If glaucoma patients have nail deformities or musculoskeletal abnormalities, nail-patella syndrome should be suspected and a multidisciplinary approach should be conducted.

Do you know this syndrome? Nail patela syndrome: a pathognomonic dermatologic finding

Abstract: The nail-patella syndrome involves a clinical tetrad of changes in the nails, knees, elbows and the presence of iliac horns. Nail changes are the most constant feature: absent, hypoplastic, or dystrophic. A pathognomonic finding is the presence of the triangular lunula. The diagnosis of nail-patella syndrome is based on clinical findings. In this paper we will discuss a case report of this syndrome and its relation with a dermatological finding.

Clinico-Genetic Study of Nail-Patella Syndrome

Nail-patella syndrome (NPS) is an autosomal dominant disease that typically involves the nails, knees, elbows and the presence of iliac horns. In addition, some patients develop glomerulopathy or adult-onset glaucoma. NPS is caused by lossof- function mutations in the LMX1B gene. In this study, phenotype-genotype correlation was analyzed in 9 unrelated Korean children with NPS and their affected family members. The probands included 5 boy and 4 girls who were confirmed to have NPS, as well as 6 of their affected parents. All of the patients (100%) had dysplastic nails, while 13 patients (86.7%) had patellar anomalies, 8 (53.3%) had iliac horns, 6 (40.0%) had elbow contracture, and 4 (26.7%) had nephropathy including one patient who developed end-stage renal disease at age 4.2. The genetic study revealed 8 different LMX1B mutations (5 missense mutations, 1 frame-shifting deletion and 2 abnormal splicing mutations), 6 of which were novel. Genotype-phenotype correlation was not identified, but inter- and intrafamilial phenotypic variability was observed. Overall, these findings are similar to the results of previously conducted studies, and the mechanism underlying the phenotypic variations and predisposing factors of the development and progression of nephropathy in NPS patients are still unknown.

A Synonymous Genetic Alteration of LMX1B in a Family with Nail-Patella Syndrome

The gene responsible for nail-patella syndrome, LMX1B, has recently been identified on chromosome 9q. Here we present a patient with nail-patella syndrome and an autosomal dominant pattern of inheritance. A 17-year-old girl visited our clinic for the evaluation and treatment of proteinuria. She had dystrophic nails, palpable iliac horns, and hypoplastic patellae. Electron microscopy of a renal biopsy showed irregular thickening of the glomerular basement membrane. A family history over three generations revealed five affected family members. Genetic analysis found a change of TCG to TCC, resulting in a synonymous alteration at codon 219 in exon 4 of the LMX1B gene in two affected family members. The same alteration was not detected in an unaffected family member. This is the first report of familial nail-patella syndrome associated with an LMX1B in Korea mutation, However, we can not completely rule out the possibility that the G-to-C change may be a single nucleotide polymorphism as this genetic mutation cause no alteration in amino acid sequence of LMX1B.

Síndrome unha-patela: Evolução da instabilidade da patela / Nail-patella syndrome: evolution of pattelar instability

A síndrome da unha-patela é uma doença de caráter autossômico dominante, com algumas características clássicas dermatológicas, músculoesqueléticas e, eventualmente, renais, oculares e gastrointestinais. Tem como principal sintoma ortopédico dor patelofemoral associada com instabilidade da patela desde a primeira infância. A melhor maneira de obter bons resultados nestes casos é um tratamento precoce da instabilidade do joelho. Tratada tardiamente, pode levar a uma artrose precoce, com limitação funcional da articulação do joelho. O presente caso mostra uma paciente que, tem se apresentado com essa síndrome, foi submetida a tratamento cirúrgico tardio e evoluiu com degeneração articular e limitação funcional do joelho. O objetivo deste trabalho é atentar para as características fenotípicas sindrômicas da doença e relacioná-las com as queixas ortopédicas comuns no consultório (tais como dor e instabilidade do joelho e, possivelmente, do cotovelo) e, finalmente, poder tratar esses sintomas precocemente, garantindo uma evolução favorável para a paciente.

The nail-patella syndrome is an autosomal dominant disease with some dermatological, musculoskeletal and, occasionally, renal, ocular and gastrointestinal classical characteristics. Its main clinical orthopaedic symptom is patellofemoral pain associated with patellar instability since early childhood. The best way to achieve good results in such cases is to establish an early treatment for knee instability, otherwise it may lead to early arthrosis and functional limitation of the knee joint. The present case describes a patient with such syndrome who underwent late surgical treatment and evolved with joint degeneration and functional limitation of the knee. The objective of this study is to consider the syndromic phenotypic features of the disease, correlate them with orthopaedic complaints commonly reported to the physician, such as pain and instability of the knee joint and maybe of the elbow joint and, finally, be able to provide an early treatment for symptoms in order to ensure a favorable evolution to the patient.

Congenital Anonychia with Ectrodactyly of 5th Finger

PURPOSE: Despite a high frequency of acquired nail disease, congenital absence of the nail, also called as anonychia, is a rare anomaly. It may be seen as an isolated of phalangeal bone(ectrodactyly), nail-patella syndrome, birth trauma, impaired peripheral circulation, alopecia areata, and pemphigus, idiopathic atrophy of the nail, bullous drug eruptions, periodic shedding, lichen planus, Stenvens-Johnson syndrome and so forth. METHODS: We have experienced a rare case of 40-day-old neonate, suffering from intrauterine growth retardation, but without familial history, chromosomal anomalies or any other diseases. RESULTS: There was no nail on left 5th finger and distal phalangeal bone of same finger. So, We diagnosed as Congenital Anonychia with ectrodactyly of 5th Finger. CONCLUSION: We report this case as congenital anonychia of 5th finger which have developed from underlying distal phalangeal ectrodactyly. We also review other reported cased in the literatures.

A Case of Nail-patella Syndrome / 대한피부과학회지

Nail-patella syndrome (NPS) is a rare autosomal dominant disorder characterized by fingernail dysplasia, hypoplastic or absent patellae, dislocation of the radial head, and bony protuberances of the iliae, also known as iliac horns. It results from a heterogenous loss of function or mutations in the transcription factor (LMX1b). Herein, we report a rare case of nail-patella syndrome in an 18 month-old female.

Cutis laxa with growth and developmental delay, wrinkly skin syndrome and gerodermia osteodysplastica: a report of two unrelated patients and a literature review

Two unrelated patients of different sexes are described, both presenting with congenital redundant skin (cutis laxa), growth deficiency, mental retardation and bone dystrophy. Parental consanguinity in both families and a more pronounced severity of the neurological disease in the male patient were present. Both patients were diagnosed in infancy as having De Barsy syndrome, but clinical follow-up revealed that the clinical picture was compatible with the diagnosis of cutis laxa with growth and developmental delay (CLGDD), gerodermia osteodysplastica (GO) and wrinkly-skin syndrome (WWS). It has recently been suggested that cutis laxa with growth and developmental delay, gerodermia osteodysplastica and wrinkly skin syndrome are the same condition. A review concerning this diagnosis is also presented.

Radiologic Findings of Nail-Patella Syndrome: Case Report

Nail-patella syndrome is a rare autosomal dominant pleiotropic disorder characterized by dysplasia of the nails, patellar aplasia or hypoplasia, iliac horns, and dysplasia or dislocation of the elbow. We experienced a case of nail-patella syndrome. NPS is a relatively uncommon disease; however, an understanding of the typical radiologic findings is useful in establishing the diagnosis and guiding the treatment.

A Case of Nail-Patella Syndrome Who Presented with Characteristic Electron Microscopic Findings / 대한신장학회잡지

Nail-patella syndrome is a relatively rare autosomal dominant disorder characterized by dysplastic nail, hypoplastic or absent patella, and dislocation of radial head and iliac horns. In addition, renal abnormalities have been reported. The usual clinical signs of the renal involvement are asymptomatic proteinuria, microscopic hematuria, and in some cases progression to end stage renal disease. We present the case of adult with nail-patella syndrome, who developed proteinuria. Electron microscopy revealed irregular thickening of the glomerular basement membrane with areas of rarefaction, giving rise to a pathognomonic "moth-eaten" appearance.

Síndrome unha-patela (onicoosteoartrodisplasia hereditária): relato de duas famílias afetadas / Nail-patella syndrome (hereditary arthro-onychodisplasia): report on two affected families

Este trabalho apresenta cinco casos de síndrome unha-patela em duas famílias distintas, envolvendo membros de até três gerações. Os cinco acometidos foram submetidos a exames clínicos e radiológicos. Em tais casos, há concordância com a literatura mundial: tétrade de sinais (distrofia ungueal, displasias do cotovelo, da pélvis e do joelho), transmissão autossômica dominante, apresentando completa penetrância com expressividade variável e ligação com o sistema sanguíneo ABO.