Rib-polydactyly Syndrome Type Research Articles

VP16.14: Diagnosis of short rib polydactyly syndrome type IV (Beemer‐Langer syndrome): a case report

Short rib-polydactyly syndrome (SRPS) is a rare congenital autosomal recessive inherited disease classified in four subtypes. Prenatal ultrasonography findings and postnatal examinations may help classify in one of four subtypes. We present a case of an infant who presented multiple congenital anomalies and the postnatal radiography helped to classify the SRPS as type IV (Beemer-Langer). A 23-year-old was referred for prenatal ultrasound which showed cystic hygroma, small omphalocele and choledocal cyst. Chromosomal analysis revealed a normal male karyotype. Morphological scan revealed small thorax, short ribs, micromelic shortening of limbs with the tibia slightly longer than the fibula, unilateral clubfoot, hidrocephalus and renal hiperechogenicity. Magnetic Resonance performed at 35 weeks revealed micrognathia and mesenteric lymphangioma. The infant delivered at 38 weeks of gestation and died within 60 minutes due to respiratory failure. Postmortem radiography showed marked shortening of all long bones, strikingly narrow thorax with short and horizontal ribs, highly placed clavicles, small scapulae, small ilia and the tibia was longer then the fibula. Identification of the SRPS subtype can be difficult due to overlap of clinical and pathologic findings. This case may help understanding Beemer-Langer type's phenotypic features such as micrognathia, cleft lip, hydrops, hydrocephalus and omphalocele. The most common radiological findings include narrow thorax with short ribs, short tubular bones, highly placed clavicle, small scapulae and ilia and bowing of radius and ulna with the tibia being longer than the fibula. The prognosis of Beemer-Langer syndrome is poor as infants usually die shortly after birth because of respiratory failure secondary to marked pulmonary hypoplasia.

A relatively mild skeletal ciliopathy phenotype consistent with cranioectodermal dysplasia is associated with a homozygous nonsynonymous mutation in WDR35.

Ciliopathies are a class of clinically and genetically heterogeneous disorders characterized by deficits of the primary cilium, an important organelle for cellular signaling and development. Here we report on a patient from a consanguineous family presenting with renal cysts, short stature, distinctive facial features, missing teeth, brachydactyly, narrow chest, and abnormal ribs. His phenotype resembled a skeletal ciliopathy and the initial clinical differential diagnosis included Jeune thoracic dystrophy and cranioectodermal dysplasia. Due to the presence of parental consanguinity, a homozygous recessive mutation was the suspected cause and homozygosity mapping was used to direct candidate gene sequencing. WDR35, an intraflagellar transport protein previously associated with cranioectodermal dysplasia, the more severe short rib polydactyly syndrome type V and recently Ellis van Creveld syndrome, is present within a region of homozygosity and sequencing of all coding exons identified a novel homozygous nonsynonymous variant, p.Trp1153Cys. This variant affects a highly conserved tryptophan residue, is predicted to be deleterious, and is the most distal mutation yet reported in WDR35. This case expands the spectrum of phenotypes caused by WDR35 mutations, which we review herein.

Majewski Syndrome, Short Rib Polydactyly Syndrome (SRPS) Type II - A Rare Case Report, with Review of Literature

Short Rib Polydactyly Syndrome (SRPS) type II also known as Majewski syndrome, is the rarest of the four subtypes of SRPS which is a rare inherited skeletal dysplasia. We report a case of Majewski syndrome in a neonate with brief review of literature. A 24 years old primigravida, with history of second degree consanguineous marriage underwent a Prenatal USG which revealed anhydramnios, bilateral enlarged kidneys, extremely narrow thorax and bilateral short limbs with polydactyly. Based on these findings a probable diagnosis of lethal skeletal dysplasia was made and termination of pregnancy advised. Refusing termination the mother delivered a male foetus at 30 weeks with severe respiratory distress and gross anomalies. The foetus succumbed to respiratory failure inspite of resuscitation. Gross findings were a male Case Study Andola et al.; BJMMR, 9(12): 1-8, 2015; Article no.BJMMR.18367 2 foetus with enlarged head, hydropic face, hypertelorism, short nose, depressed nasal bridge, pseudo cleft lip, cleft palate, low set posterior rotated ears, cystic hygroma, micrognathia, short and narrow chest, all the limbs showed mesomelic limb shortening, postaxial polydactyly, syndactyly and brachydactyly. Postnatal X-ray, CT scan and USG confirmed the above mentioned features and additional findings were extremely short horizontal ribs and disproportionately shortened ovoid tibia. Autopsy revealed a bell shaped thorax, small hypoplastic lungs, bilateral enlarged kidneys, atrial septal defect, hypoplastic epiglottis and larynx and short small intestine. Microscopic findings of pulmonary hypoplasia, renal cystic dysplasia, hepatic fibrosis and markedly retarded endochondral ossification correlate with the clinical, radiological and pathological findings of Short Rib Polydactyly Syndrome Type II -Majewski Syndrome.

Prenatal diagnosis and molecular genetic analysis of short rib-polydactyly syndrome type III (Verma-Naumoff) in a second-trimester fetus with a homozygous splice site mutation in intron 4 in the NEK1 gene

ObjectiveTo demonstrate perinatal imaging findings and to investigate the mutation in the NEK1 gene in a fetus with type III short rib-polydactyly syndrome (SRPS) (Verma-Naumoff). Case ReportA 34-year-old woman with no past history of fetal SRPS was referred to the hospital at 21 weeks of gestation because of sonographic diagnosis of short limbs in the fetus. Fetal ultrasound revealed a narrow thorax, short ribs, short limbs with marginal spurs, and postaxial hexadactyly in both the hands and feet. A diagnosis of SRPS III (Verma-Naumoff) was made. Amniocentesis was performed. The karyotype was 46,XY. Molecular genetic analysis of the amniotic fluid cells identified a homozygous splice site mutation in intron 4 (c.331-1 A > G) or IVS4-1 A > G in the NEK1 gene. The parents were heterozygous for the mutation. The pregnancy was subsequently terminated and a malformed fetus was delivered with prominent forehead, a flattened nasal bridge, a narrow and short trunk, a protuberant abdomen, bilateral postaxial polydactyly and syndactyly of the hands and feet, and micromelic limbs. No facial cleft or genital abnormality was noted. The radiograph was consistent with SRPS III. ConclusionPolydactyly, micromelia, metaphyseal spurs, widened humeral metaphyses, and shortened ribs can be prominent prenatal ultrasound findings of SRPS III. The present case provides evidence for a correlation of a mutation in the NEK1 gene with SRPS III.

Short rib-polydactyly syndrome type II (Majewski): Prenatal diagnosis, perinatal imaging findings and molecular analysis of the NEK1 gene

ObjectiveTo demonstrate perinatal imaging findings and to investigate the mutation in the NEK1 gene in a fetus with type II short rib-polydactyly syndrome (SRPS) (Majewski). Case ReportA 34-year-old woman with a past history of fetal SRPS was referred to the hospital at 16 weeks of gestation because of sonographic diagnosis of short limbs in the fetus. Fetal ultrasound revealed short ribs, short limbs, absence of tibiae, polydactyly, syndactyly and choroid plexus cysts. At 21 weeks of gestation, polycystic kidneys were found. The pregnancy was terminated, and a fetus was delivered with facial dysmorphism, a median cleft lip, a narrow chest, micromelia, aplasia of tibiae, hypoplastic nails, syndactyly and postaxial polydactyly. The karyotype was 46,XX. Molecular analysis of fetal tissues showed a paternal-origin heterozygous splice site mutation in intron 7 (c.465-1 G>A) in the NEK1 gene, but no mutations in the genes of WDR35, DYNC2H1, IFT80, EVC and EVC2. The NEK1 mutation causes an alteration of the splice acceptor site of intron 7 (IVS7-1 G>A). No second mutation was identified. ConclusionTibial aplasia, choroid plexus cysts and polycystic kidneys can be prominent prenatal ultrasound findings of type II SRPS. The present case provides evidence for a correlation of NEK1 mutation with type II SRPS.

Diagnosis of short rib polydactyly syndrome type IV (Beemer–Langer syndrome) with cystic hygroma: A case report

Short rib polydactyly syndrome (SRPS) is a very rare congenital autosomal recessive inherited disease, classified into four subtypes. It has distinct imaging findings on prenatal sonography (US) and ancillary findings on both pre- and postnatal examinations may help classify individual cases into one of four subtypes. We report the US findings in a case of SRPS type IV (Beemer-Langer dysplasia) in a male fetus with multiple congenital anomalies, including cystic hygroma. The postnatal ultrasound, radiographic, and postmortem examinations helped to classify the SRPS as type IV. We believe this is the first documented case associating cystic hygroma and polydactyly.

Ciliary Abnormalities Due to Defects in the Retrograde Transport Protein DYNC2H1 in Short-Rib Polydactyly Syndrome

The short-rib polydactyly (SRP) syndromes are a heterogeneous group of perinatal lethal skeletal disorders with polydactyly and multisystem organ abnormalities. Homozygosity by descent mapping in a consanguineous SRP family identified a genomic region that contained DYNC2H1, a cytoplasmic dynein involved in retrograde transport in the cilium. Affected individuals in the family were homozygous for an exon 12 missense mutation that predicted the amino acid substitution R587C. Compound heterozygosity for one missense and one null mutation was identified in two additional nonconsanguineous SRP families. Cultured chondrocytes from affected individuals showed morphologically abnormal, shortened cilia. In addition, the chondrocytes showed abnormal cytoskeletal microtubule architecture, implicating an altered microtubule network as part of the disease process. These findings establish SRP as a cilia disorder and demonstrate that DYNC2H1 is essential for skeletogenesis and growth.

Orofaciodigital Syndrome Type IV (Mohr-Majewski Syndrome): Report of a Family with Two Affected Siblings

We report on sibling fetuses with orofaciodigital syndrome (OFDS) type IV (Mohr-Majewski syndrome). The 1st was a 13-week-old fetus with hypertelorism; a median cleft defect of the upper lip, soft palate, and uvula; a polypoid lower lip and multiple frenula of the tongue adherent to the mandible; a congenital heart defect; pre- and postaxial polydactyly of the upper and preaxial polydactyly of the lower limbs; and an intersex genitalia. However, the shortening of both arms and forearms was particularly striking, with shortening of the ulna and ulnar deviation of both hands. The 2nd fetus was of the same parents, was 11 weeks old, and presented with a similar spectrum of malformations. The features of both fetuses showed a transitional phenotype between the OFDS type II (Mohr syndrome) and the short rib-polydactyly syndrome type II (Majewski syndrome), thus extending the known spectrum of the OFDS type IV.

Recurrence of short rib polydactyly syndrome – a rare skeletal dysplasia

A case of short rib polydactyly syndrome type I-Saldino Noonan was diagnosed in three successive pregnancies from a non consanguineous couple. Short limbs, short ribs, polydactyly, with visceral anomalies were noted and confirmed on autopsy.

Cardiac malformation in two infants with hypochondrogenesis

Autopsy records from the Women and Infants' Hospital from January 1974 through January 1994 were reviewed to identify cardiac malformations in the presence of skeletal dysplasia. Of 24 cases of lethal fetal or neonatal osteochondrodysplasias, 4 were given diagnoses in which disorders of type II collagen are regarded as causative. These 4 were categorized in the spondyloepiphyseal dysplasia (SED) spectrum of disorders; specifically two patients with hypochondrogenesis and two with spondyloepiphyseal dysplasia congenita were identified. Defects in cardiac septation were noted in the 2 patients with hypochondrogenesis. No cardiovascular abnormalities were present in the remaining cases, which included thanatophoric dysplasia, osteogenesis imperfecta, and asphyxiating thoracic dystrophy. Although cardiovascular malformations have been described in other types of osteochondrodysplasias, e.g., short rib polydactyly syndrome type II and chondroectodermal (Ellis-van Creveld) dysplasia, congenital heart disease has not been described in hypochondrogenesis. Type II collagen, which has been found to be abnormal in some patients with hypochondrogenesis, is considered to have a limited tissue distribution, and has not been detected as yet in human myocardium. The findings presented here suggest that type II collagen may function in human cardiogenesis.

Prenatal sonographic diagnosis of short rib-polydactyly syndrome type II, Majewski type

Prenatal sonographic diagnosis of short rib-polydactyly syndrome type II, Majewski type

Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrome spectrum: a clinicopathologic study.

Clinicopathologic examination of eight patients with asphyxiating thoracic dysplasia (Jeune; ATD) disclosed two different types, which were designated as type 1 and type 2. Type 1 ATD was characterized by the presence of radiologically irregular metaphyseal ends and histopathologically irregular cartilage bone junction with patchy distribution of physeal zone of hypertrophy. Type 2 ATD showed radiologically smooth metaphyseal ends and histopathologically diffusely retarded and disorganized physes with smooth cartilage bone junctions. Examination of four patients with the "Verma-Naumoff" short rib-polydactyly syndrome showed many radiologic and pathologic features similar to those of type 1 ATD. Differential diagnosis of these three osteochondrodysplasias is discussed along with chondroectodermal dysplasia (Ellis-van Creveld), short rib-polydactyly syndrome type 1 (Saldino-Noonan), short rib-polydactyly syndrome type 2 (Majewski), and the new short rib syndrome reported by Beemer et al [1983].

Antenatal detection of recurrence of Majewski dwarf (short rib-polydactyly syndrome type II Majewski)

Two cases of Majewski dwarfism are reported. both were the product of the same non-consanguinous marriage and each exhibited the key features of this syndrome: polysyndactyly, short ribs, cleft lip, disproportionately short tibiae and a normal pelvis. The first infant, a baby boy, died shortly after birth, whilst the second was detected prenatally by ultrasound and had female characteristics. Several skeletal dysplasias have been demonstrated in utero by ultrasound, but we believe this to be the first reported case of a Majewski dwarf detected by this method. In view of the difficulty in diagnosis of this syndrome comparison is made with other short rib-polydactyly syndromes.