RESUMEN
Majewski Osteodysplastic Primordial Dwarfism, Type II (MOPD II) is a rare, autosomal recessive disorder. Features include severe intrauterine growth retardation (IUGR), poor postnatal growth (adult stature approximately 100 cm), severe microcephaly, skeletal dysplasia, characteristic facial features, and normal or near normal intelligence. An Institutional Review Board (IRB) approved registry was created and currently follows 25 patients with a diagnosis of MOPD II. Based on previous studies, a neurovascular screening program was implemented and 13 (52%) of these patients have been found to have cerebral neurovascular abnormalities including moyamoya angiopathy and/or intracranial aneurysms. The typical moyamoya pathogenesis begins with vessel narrowing in the supraclinoid internal carotid artery, anterior cerebral (A1) or middle cerebral (M1) artery segments. The narrowing may predominate initially on one side, progresses to bilateral stenosis, with subsequent occlusion of the vessels and collateral formation. We present four patients who, on neurovascular screening, were found to have cerebrovascular changes. Two were asymptomatic, one presented with a severe headache and projectile vomiting related to a ruptured aneurysm, and one presented after an apparent decline in cognitive functioning. Analysis of the registry suggests screening for moyamoya disease be performed at the time of MOPD II diagnosis and at least every 12-18 months using MRA or computerized tomographic angiography (CTA). We believe this is imperative. If diagnosed early enough, re-vascularization and aneurysm treatment in skilled hands can be performed safely and prevent or minimize long-term sequelae in this population. Emergent evaluation is also needed when other neurologic or cardiac symptoms are present.
Asunto(s)
Enanismo/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/patología , Adolescente , Niño , Preescolar , Constricción Patológica/complicaciones , Angiografía Coronaria , Enanismo/patología , Humanos , Lactante , Angiografía por Resonancia Magnética , Masculino , Fenotipo , Síndrome de Costilla Pequeña y Polidactilia/patologíaRESUMEN
INTRODUCTION: KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities. PATIENT CONCERNS: Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies. DIAGNOSIS: A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly. INTERVENTION: Patients were transferred to neonatal intensive care unit and received life-support treatment. OUTCOMES: Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease. CONCLUSION: We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.
Asunto(s)
Proteínas de Ciclo Celular/genética , Síndromes Orofaciodigitales/complicaciones , Síndromes Orofaciodigitales/genética , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/genética , Ciliopatías , Humanos , Recién Nacido , Italia , Masculino , Fenotipo , Romaní , HermanosRESUMEN
We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome. At age 3 years, he became paralyzed due to a cerebrovascular malformation. Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the patient's lymphoblastoid cell line lysate showed the absence of the protein pericentrin. Subsequent molecular analysis identified a novel homozygous single base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in the development of cerebral vessels is suggested.
Asunto(s)
Antígenos/genética , Enanismo/complicaciones , Enanismo/diagnóstico , Mutación/genética , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/diagnóstico , Adulto , Secuencia de Bases , Western Blotting , Huesos/diagnóstico por imagen , Encéfalo/patología , Estudios de Casos y Controles , Preescolar , Análisis Mutacional de ADN , Diagnóstico Diferencial , Enanismo/diagnóstico por imagen , Femenino , Humanos , Lactante , Recién Nacido , Angiografía por Resonancia Magnética , Masculino , Datos de Secuencia Molecular , Embarazo , Radiografía , Síndrome de Costilla Pequeña y Polidactilia/diagnóstico por imagen , SíndromeRESUMEN
We describe two patients with short rib-polydactyly syndrome (SRPS) from two unrelated Spanish families. These patients present clinical and radiological characteristics that overlap those of the different established types of SRPS. In addition, one patient had anencephaly and the other patient had severe brain abnormalities with a family history of an older sister with anencephaly, and a brother diagnosed with SRPS. This second family is interesting in that the two affected brothers present with different clinical and radiological findings; for example, one had ovoid tibiae and the other did not. This particular family shows that intrafamiliar variation is also observed within SRPS. It remains unsettled whether these cases might be considered a new type of SRPS or a variant of an established entity or whether the differences between the SRPS represent variability or heterogeneity. Molecular studies may answer this question in the near future.
Asunto(s)
Anencefalia/complicaciones , Sistema Nervioso Central/anomalías , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Anencefalia/genética , Muerte Fetal/genética , Humanos , Masculino , Fenotipo , Radiografía , Síndrome de Costilla Pequeña y Polidactilia/diagnóstico por imagen , Síndrome de Costilla Pequeña y Polidactilia/genéticaRESUMEN
We present 2 unrelated fetuses with manifestations of both the hydrolethalus syndrome and the short rib-polydactyly syndrome, type Majewski. It is proposed that cases of hydrolethalus syndrome with short limbs constitute a separate type of lethal osteochondrodysplasia mimicking short rib-polydactyly syndromes.
Asunto(s)
Hidrocefalia/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Adulto , Femenino , Feto/patología , Humanos , Hidrocefalia/genética , Hidrocefalia/patología , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Fenotipo , Embarazo , Síndrome de Costilla Pequeña y Polidactilia/genética , Síndrome de Costilla Pequeña y Polidactilia/patología , SíndromeRESUMEN
A stillborn baby boy had findings of severe constitutional dwarfism with short limbs, short ribs, and polydactyly that were consistent with Naumoff (type III) short-rib polydactyly syndrome. He also had additional congenital anomalies, including cleft palate, notching of the upper lip, small tongue with accessory sublingual tissue. These oral and pharyngeal anomalies were consistent with Mohr (type II) oral-facial-digital syndrome. We suggest the stillborn infant represented a compound of Naumoff short-rib polydactyly syndrome (SRPS-III) and Mohr oral-facial-digital syndrome (OFDS-II).
Asunto(s)
Síndromes Orofaciodigitales/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Resultado Fatal , Humanos , Recién Nacido , MasculinoRESUMEN
Osteochondrodysplasias are hereditary dysfunctions of the enchondral ossification with a decreased longitudinal bone-growth. We describe the case of a female child which suffered from a short rib-polydactyly-syndrome, a localised form of a osteo-chondrodysplasia, and died at the age of nine months as a result of the typical complications of this disease.
Asunto(s)
Displasia Broncopulmonar/patología , Pulmón/patología , Insuficiencia Respiratoria/patología , Costillas/patología , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Síndrome de Costilla Pequeña y Polidactilia/patologíaRESUMEN
A case of atypical short-rib polydactyly syndrome (Majewski) with severe cerebral malformations (infundibular hamartoma, Dandy-Walker cyst, aplasia of cerebellar vermis, etc.) is reported. This seems to be the first case so far described in the literature.
Asunto(s)
Cerebelo/anomalías , Osteocondrodisplasias/patología , Síndrome de Costilla Pequeña y Polidactilia/patología , Cerebelo/patología , Síndrome de Dandy-Walker/patología , Hamartoma/patología , Humanos , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/patología , Masculino , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/diagnósticoRESUMEN
An 18-year-old gravida 1 para 0 female was presented at 35 weeks' gestation with severe oligohydramnios. Sonography revealed a fetus with hydrops, bilaterally enlarged echogenic kidneys, and short extremities. The infant died at birth and autopsy was compatible with short-rib polydactyly syndrome type II, Majewski type. Renal histology was consistent with glomerulocystic disease.
Asunto(s)
Enfermedades Fetales/diagnóstico por imagen , Enfermedades Renales Quísticas/diagnóstico por imagen , Síndrome de Costilla Pequeña y Polidactilia/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Femenino , Humanos , Enfermedades Renales Quísticas/complicaciones , Enfermedades Renales Quísticas/embriología , Glomérulos Renales/diagnóstico por imagen , Embarazo , Síndrome de Costilla Pequeña y Polidactilia/complicaciones , Síndrome de Costilla Pequeña y Polidactilia/embriologíaRESUMEN
Short rib-polydactyly syndrome (SRPS) is manifested by short-limb dwarfism, short ribs with thoracic hypoplasia, and polydactyly. This inheritable syndrome has distinct imaging findings on prenatal sonography, and ancillary findings on both pre- and postnatal assessments may enable individual cases to be classified into 1 of 4 subtypes. In this report, we present a recurrent case of SRPS that was associated with a cystic hygroma and choroid plexus cysts. Although cystic hygromas are not uncommonly seen in skeletal dysplasias, the presence of concomitant cystic hygroma and choroid plexus cysts suggests a chromosomal abnormality such as trisomy 18.