RESUMEN

Langer-Giedion syndrome (LGS) is caused by a contiguous deletion at 8q23q24, characterized by exostoses, facial, ectodermal, and skeletal anomalies, and, occasionally, intellectual disability. LGS patients have been diagnosed clinically or by routine cytogenetic techniques, hampering the definition of an accurate genotype-phenotype correlation for the syndrome. We report two unrelated patients with 8q23q24 deletions, characterized by cytogenomic techniques, with one of them, to our knowledge, carrying the smallest deletion reported in classic LGS cases. We assessed the pathogenicity of the deletion of genes within the 8q23q24 region and reviewed other molecularly confirmed cases from the literature. Our findings suggest a 3.2-Mb critical region for a typical presentation of the syndrome, emphasizing the contribution of the TRPS1, RAD21, and EXT1 genes' haploinsufficiency, and facial dysmorphisms as well as bone anomalies as the most frequent features among patients with LGS. We also suggest a possible role for the CSMD3 gene, whose deletion seems to contribute to central nervous system anomalies. Since studies performing such correlation for LGS patients are limited, our data contribute to improving the ge-notype-phenotype characterization for LGS patients.

Asunto(s)

Síndrome de Langer-Giedion , Deleción Cromosómica , Cromosomas Humanos Par 8 , Hibridación Genómica Comparativa , Estudios de Asociación Genética , Haploinsuficiencia , Humanos , Síndrome de Langer-Giedion/diagnóstico , Síndrome de Langer-Giedion/genética , Fenotipo , Proteínas Represoras/genética

RESUMEN

Kenny-Caffey syndrome (KCS) is a rare hereditary skeletal disorder involving hypoparathyroidism. The autosomal dominant form (KCS2), caused by heterozygous pathogenic variants in the FAM111A gene, is distinguished from the autosomal recessive form (KCS1) and Sanjad-Sakati syndrome (SSS), both caused by pathogenic variants in the tubulin folding cofactor E (TBCE) gene, by the absence of microcephaly and intellectual disability. We present a patient with KCS2 caused by a de novo pathogenic variant c.1706G>A (p.Arg569His) in FAM111A gene, presenting intellectual disability and microcephaly, which are considered to be typical signs of SSS. We suggest that KCS1, KCS2, and SSS may not represent mutually exclusive clinical entities, but possibly an overlapping spectrum.

Asunto(s)

Anomalías Múltiples/patología , Enanismo/patología , Trastornos del Crecimiento/patología , Hiperostosis Cortical Congénita/patología , Hipocalcemia/patología , Hipoparatiroidismo/patología , Discapacidad Intelectual/patología , Mutación , Osteocondrodisplasias/patología , Fenotipo , Receptores Virales/genética , Convulsiones/patología , Anomalías Múltiples/genética , Adolescente , Enanismo/complicaciones , Enanismo/genética , Trastornos del Crecimiento/complicaciones , Trastornos del Crecimiento/genética , Humanos , Hiperostosis Cortical Congénita/complicaciones , Hiperostosis Cortical Congénita/genética , Hipocalcemia/complicaciones , Hipocalcemia/genética , Hipoparatiroidismo/complicaciones , Hipoparatiroidismo/genética , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/genética , Masculino , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/genética , Convulsiones/complicaciones , Convulsiones/genética

RESUMEN

Schmid metaphyseal chondrodysplasia is a rare genetic cause of skeletal dysplasia. Patients usually present skeletal abnormalities but no major visceral malformations or intellectual disability. We report a case of a 2-year-old male patient with short stature, progressive genu varum, and waddling gait. Radiographic findings were essential to guide investigation and molecular confirmation, allowing proper treatment and genetic counseling.

RESUMEN

Congenital hypothyroidism is a clinical emergency due to its potential risk of mental retardation. Constipation might be present in hypothyroid children. However, Hirschsprung disease is rarely associated with congenital hypothyroidism. Herein, a case of congenital hypothyroidism in a one-year-old child mimicking Hirschsprung disease is described. Adequate treatment with levothyroxine sodium tablets controlled intestinal dysmotility that mimicked congenital intestinal aganglionosis due to the critical influence of thyroid hormones on bowel motility.

RESUMEN

Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed.