Condrodisplasia punctata ligada ao cromossomo X tipo 1 (CDPX1) - relato de caso com fenótipo atípico / X-linked chondrodysplasia punctata type 1 (CDPX1) - case report with atypical phenotype

A condrodisplasia punctata (CDP) é um grupo de displasias ósseas caracterizadas por calcificações puntiformes nas cartilagens, principalmente epifisárias. Entre as várias formas de CDP, a ligada ao X é rara e foi descrita em 50 pacientes do sexo masculino na literatura. O objetivo deste estudo é descrever um caso atípico de CDPX1 e compará-lo com a literatura prévia. Pré-escolar, sexo masculino, quatro anos, nascido a termo, pequeno para a idade gestacional e sem casos semelhantes na família. Ele evoluiu com baixa estatura desproporcionada, eutrofia, escoliose cervical e dorsal com pectus carinatum, assimetria discreta em membros inferiores, hipertelorismo ocular com esclera azul-acinzentada e queda de cabelo. Não apresentou fraturas ou dores ósseas e teve desenvolvimento neuropsicomotor adequado para a idade. Os exames não mostraram alterações no perfil osteometabólico nem nos hormônios hipofisários. O cariótipo foi 46,XY e o painel genético para displasias esqueléticas mostrou uma variante patogênica em hemizigose no gene ARSL (Arylsulfatase L) chrX:2.934.859 C>T (p.Trp581* ENST00000381134) com diagnóstico de condrodisplasia punctata ligada ao cromossomo X do tipo 1. A CDPX1 está diretamente relacionada à deficiência da atividade da enzima ARSL, o que pode resultar em alterações de desenvolvimento neuropsicomotor, perda auditiva e episódios de insuficiência respiratória. No entanto, estas características não foram apresentadas pelo probando. Assim, o probando apresenta uma forma mais branda de CDPX1. O diagnóstico precoce de displasias esqueléticas como a CDPX1 é importante para o acompanhamento ambulatorial adequado, aconselhamento familiar e prevenção do desenvolvimento de comorbidades a longo prazo.

Chondrodysplasia punctata (CDP) is a group of bone dysplasias characterized by punctate calcifications in the cartilage, mainly epiphyseal. Among the various forms of CDP, the X-linked form is rare and has been described in 50 male patients in the literature. The aim of this study is to describe an atypical case of CDPX1 and compare it with previous literature. Preschooler, male, four years old, born full-term, small for gestational age and with no similar cases in the family. He developed disproportionate short stature, eutrophy, cervical and dorsal scoliosis with pectus carinatum, slight asymmetry in the lower limbs, ocular hypertelorism with blue-gray sclera and hair loss. He did not present fractures or bone pain and had neuropsychomotor development appropriate for his age. The exams showed no changes in the osteometabolic profile or in pituitary hormones. The karyotype was 46,XY and the genetic panel for skeletal dysplasias showed a hemizygous pathogenic variant in the ARSL gene (Arylsulfatase L) chrX:2.934.859 C>T (p.Trp581* ENST00000381134) diagnosed with X-linked chondrodysplasia punctata type 1. CDPX1 is directly related to the deficiency of ARSL enzyme activity, which can result in changes in neuropsychomotor development, hearing loss and episodes of respiratory failure. However, these characteristics were not presented by the proband. Thus, the proband has a milder form of CDPX1. Early diagnosis of skeletal dysplasias such as CDPX1 is important for adequate outpatient follow-up, family counseling and prevention of the development of long-term comorbidities.

X-linked dominant chondrodysplasia punctata 2 with severe phenotype in one female fetus: a case report / 中华围产医学杂志

We reported a female fetus diagnosed with X-linked dominant chondrodysplasia punctata 2 with severe phenotype. The fetus was found with abnormal short limbs, thick metaphysis on the right lower limb and a narrow and small thorax by prenatal ultrasound at 24+5 weeks of gestation. Non-invasive prenatal test indicated the risks of trisomies 21, 18 and 13 were low. The pregnancy was terminated at 27 weeks of gestation and postnatal X-ray imaging showed that the fetus had short femur and humerus, a narrow and small thorax, thickened metaphysis with a "splashed paint spot" pattern, and asymmetric shortened lower limbs. Whole-exome analysis showed that the fetus carried a heterozygous pathogenic mutation c.440G>A (p.Arg147His) in the EBP gene. The mutation was confirmed to be a de novo mutation as neither of her parents carried the same mutation. Thus, the patient was diagnosed as having X-linked dominant chondrodysplasia punctata 2. The severe phenotype of this case migh be related to random X chromosome inactivation.

Identification of a Novel Nonsense Mutation in the ARSE Gene of a Patient with X-Linked Recessive Chondrodysplasia Punctata

X-linked recessive chondrodysplasia punctata (CDPX1) is caused by a hemizygous mutation in the arylsulfatase E (ARSE) gene located on chromosome Xp22.3. It is a rare congenital disorder of punctate calcifications in cartilages, leading to short stature and facial and limb anomalies. These clinical features are frequently observed in all types of chondrodysplasia punctata and have also been seen in other cartilage developmental disorders. Because of the phenotypical similarities, specific testing for only one gene is inefficient and time consuming. The advent of next-generation sequencing has provided an opportunity to improve diagnostic accuracy as well as save on time and cost. Here, we report on a patient diagnosed with CDPX1, who was identified via diagnostic exome sequencing to have a novel nonsense mutation in the ARSE gene, that was inherited from the mother.

Rhizomelic chondrodysplasia punctata: A missed opportunity for early diagnosis.

A male neonate was born with rhizomelic shortening of limbs. Skeletal radiograph showed punctate calcification of epiphysis of humerus, femur, and tibia. The diagnosis and a brief review of literature pertaining to the condition with emphasis on antenatal diagnosis and counseling are being reported.

A Case of 9.7 Mb Terminal Xp Deletion Including OA1 Locus Associated with Contiguous Gene Syndrome

Terminal or interstitial deletions of Xp (Xp22.2-->Xpter) in males have been recognized as a cause of contiguous gene syndromes showing variable association of apparently unrelated clinical manifestations such as Leri-Weill dyschondrosteosis (SHOX), chondrodysplasia punctata (CDPX1), mental retardation (NLGN4), ichthyosis (STS), Kallmann syndrome (KAL1), and ocular albinism (GPR143). Here we present a case of a 13.5 yr old boy and sister with a same terminal deletion of Xp22.2 resulting in the absence of genes from the telomere of Xp to GPR143 of Xp22. The boy manifested the findings of all of the disorders mentioned above. We began a testosterone enanthate monthly replacement therapy. His sister, 11 yr old, manifested only Leri-Weill dyschondrosteosis, and had engaged in growth hormone therapy for 3 yr. To the best of our knowledge, this is the first report of a male with a 9.7 Mb terminal Xp deletion including the OA1 locus in Korea.

Condrodisplasia Rizomélica Punctata: Reporte de 2 casos

La condrodisplasia rizomélica punctata es una enfermedad peroxisomal que se transmite de manera autosómica recesiva, donde se ve afectada la actividad bioquímica de este organillo por defectos en la síntesis y actividad de enzimas que participan en una gran variedad de vías metabólicas, éstas incluyen; La beta oxidación ácidos grasos, síntesis de ácidos biliares y los compuestos isoprenoides. Describimos las manifestaciones clínicas, estudios complementarios y la evolución de dos hermanos atendidos, los cuales presentaban antecedentes y hallazgos en común con este infrecuente padecimiento. De los dos casos, uno fue del sexo femenino y el otro del sexo masculino, el primero falleció por falla respiratoria y el segundo se le realizan los estudios complementarios para el diagnóstico. Desde el punto de vista genético hay consanguinidad del cuarto grado en esta descendencia ya que la pareja son primos y esto aumenta el riesgo de que aparezcan enfermedades hereditarias del tipo autosómico recesivo.

The rhizomelic chondrodysplasia punctata is a peroxisomal disease that is transmitted in an autosomal recessive, where it affected the biochemical activity of this organelle by defects in the synthesis and activity of enzymes involved in a variety of metabolic pathways including the beta oxidation of some fatty acids, bile acid synthesis and isoprenoid compounds. This article describes the clinical manifestations, complementary studies and evolution of 2 brothers served in the Hospital José Domingo de Obaldía in 2009, which had a history and findings in common with this rare condition. Of the 2 cases, one was female and one male, the first died of a respiratory problem and the second study was performed to verify the diagnosis. From the genetic point of view there is a 4th degree consanguinity in the offspring as the pair are cousins and this increases the risk of emerging diseases of autosomal recessive hereditary.

Binder Syndrome Infant Born from Mother with Cholelithiasis / 대한소아내분비학회지

Binder syndrome is a maxillonasal dysostosis characterized by midface and nasal hypoplasia. It is sometimes associated with short terminal phalanges of fingers and toes and transient radiological features of chondrodysplasia punctata. It is associated with vitamin K deficiency during pregnancy. We describe here a baby with Binder syndrome who was born from mother with cholelithiasis during pregnancy.

A Case of X-linked Dominant Chondrodysplasia Punctata / 대한피부과학회지

X-linked dominant chondrodysplasia punctata is a rare congenital disorder characterized by transient punctate epiphyseal calcifications and ichthyotic skin changes, usually resolving during early infancy. We experienced a baby girl born with a thickened and diffusely red integument with adherent scales following the lines of Blaschko and punctata calcification, flat nose. We report a case of condrodysplasia punctata, X-linked dominant type which was confirmed with gene study.

A Case of Chondrodysplasia Punctata / 대한산부인과학회잡지

Chondrodysplasia Punctata is a rare congenital disorder of bone in infant, which is characterized by radiographic manifestation of premature deposition of punctata calcific density in epiphyseal areas, preformed in cartilage. Chondrodysplasia Punctata includes two different disorders: a rhizomelic, potentially lethal variety and a nonrhizomelic variety (Conradi-Hunermann syndrome) which is more common and generally benign. These two conditions have different clinical, genetic, and radiographic characteristics. We experienced a case of rhizomelic Chondrodysplasia Punctata (RCDP) in a fetus of intrauterine pregnancy at 19 weeks who was terminated because of ultrasonographic demonstration of gross skeletal and midfacial anomaly. Thus, we report a case with brief review of the literature.

A Case of Rhizomelic Chondrodysplasia Punctata Occurring in Siblings / 소아과

Chondrodysplasia punctata is a group of heterogeneous bone dysplasia characterized by punctate calcifications of the cartilage, frequently associated with a shortening of the limbs, cataracts, icthyosis and alopecia, alterations of the nervous system, and mental and growth deficiencies. Our case presented findings of the rhizomelic chodrodysplasia punctata : a characteristic face, a sucking difficulty and a short neck. Skeletal radiographies showed punctate calcification and stippling on femurs, lumbar vertebral bodies and vertebral coronal cleft. According to his family history, his brother, who had the same characteristic face and punctate calcification at the neonatal period, died at the age of six months due to respiratory failure. The rhizomelic form of chondrodysplasia puntata is rare, the prognosis is bad and death usually occurs within the first year of age. We report a case of rhizomelic chondrodysplasia punctata occurring in siblings diagnosed by clinical and radiological criteria.

A Case of Chondrodysplasia Punctata Combined with Unilateral Choanal Atresia / 대한이비인후과학회지

Chondrodysplasia punctata is a rare congenital disease. It is classified into four main types according to the clinical features and heredity: autosomal dominant (Conradi-Hunermann's) type, autosomal recessive (rhizomelic) type, X-linked dominant type and X-linked recessive type. Among the four, rhizomelic chondrodysplasia punctata (RCDP) is the most lethal form of the disease, and most patients die in the neonatal period. Diagnosis of the RCDP relies on its characteristic features and radiological finding. The characteristic features are craniofacial dysmorphism (flat face, flat nasal bridge, anteverted nostril, telecanthus), cataracts, rhizomelic limb shortening, ichthyosis, and mental retardation. Radiologic findings include rhizomelic symmetrical shortening of upper or lower extremity, coronal cleft of vertebral body, metaphysical spraying and stippled calcification. This case shows typical abnormality in the face and extremity and also radiologic abnormality, uniquely combined with unilateral choanal atresia.

Nonrhizomelic Type of Chondrodysplasia Punctata Suspected in the Brothers

Chondrodysplasia punctata is a heterogenous skeletal dysplasia characterized by small focal calcifications in articular and other cartilages in infancy, with subsequent epiphysial dysplasia and associated anomalies of the face, eyes, and skin. Chondrodysplasia punctata is classified with autosomal recessive rhizomelic type, autosomal dominant nonrhizomelic type(Conradi-Hunermann type), and X-linked dominant type. These types have different clinical manifestations respectively. We report cases of autosomal dominant type of chondrodysplasia punctata which occurred in brothers, who were presented with typical face(short collumella leading to depressed tip of the nose), punctate calcification on the lumbar spine, dislocation of right hip, no obvious skin lesions, and atropic optic nerve without cataracts.

Chondrodysplasia Punctata(Rhizomelic Type) Associated with Pneumothorax

Chondrodysplasia punctata is a rare congenital syndrome caused by a peroxisomal dysfunction. Chondrodysplasia punctata is classified into four main types-Coradi-Hunermann's type, rhizomelic type, X-linked dominant form and X-linked recessive form. A male patient with this condition was born at 39 weeks gestation, the pregnancy being complicated by polyhydroamnios, breech presentation, and anomalies of congenital limbs. At delivery, there was no activity and no initial crying. Physical examination revealed a flat nose, a short neck, scaled ichthyolytic skin, and bilaterally symmetrical shortening of the upper and lower extremities. Choromosomal analysis revealed a 46, XY karyotype. Radiologic examination disclosed stippling of the cartilage on the epiphyseal regions of the long bones, paravertebral regions, carpal bones and tarsal bones. In additions, a chest x-ray showed right pneumothorax. Chest and endotracheal tubes were inserted. However, the patient died due to respiratory failure at 19 days of life. We report a case of rhizomelic type of chondrodysplasia punctata assocoated with pneumothorax with a brief review of the related literatures.