RESUMEN
Pathogenic variants in RASA1 are typically associated with a clinical condition called "capillary malformation-arteriovenous malformation" (CM-AVM) syndrome, an autosomal dominant genetic disease characterized by a broad phenotypic variability, even within families. In CM-AVM syndrome, multifocal capillary and arteriovenous malformations are mainly localized in the central nervous system, spine and skin. Although CM-AVM syndrome has been widely described in the literature, only 21 cases with prenatal onset of clinical features have been reported thus far. Here, we report four pediatric cases of molecularly confirmed CM-AVM syndrome which manifested during the prenatal period. Polyhydramnios, non-immune hydrops fetalis and chylothorax are only a few possible aspects of this condition, but a correct interpretation of these prenatal signs is essential due to the possible fatal consequences of unrecognized encephalic and thoracoabdominal deep vascular malformations in newborns and in family members carrying the same RASA1 variant.
Asunto(s)
Malformaciones Arteriovenosas , Mancha Vino de Oporto , Femenino , Humanos , Recién Nacido , Niño , Embarazo , Mutación , Proteína Activadora de GTPasa p120/genética , Mancha Vino de Oporto/genética , Mancha Vino de Oporto/diagnóstico , Mancha Vino de Oporto/patología , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/genética , Proteínas Activadoras de GTPasa/genéticaRESUMEN
The Simpson-Golabi-Behmel syndrome type 1 (SGBS1, OMIM #312870) is an X-linked overgrowth condition comprising abnormal facial appearance, supernumerary nipples, congenital heart defects, polydactyly, fingernail hypoplasia, increased risk of neonatal death and of neoplasia. It is caused by mutation/deletion of the GPC3 gene. We describe a macrosomic 27-week preterm newborn with SGBS1 who presents a novel GPC3 mutation and emphasize the phenotypic aspects which allow a correct diagnosis neonatally in particular the rib malformations, hypoplasia of index finger and of the same fingernail, and 2nd-3rd finger syndactyly.
Asunto(s)
Arritmias Cardíacas/diagnóstico , Dedos/anomalías , Gigantismo/diagnóstico , Cardiopatías Congénitas/diagnóstico , Discapacidad Intelectual/diagnóstico , Uñas Malformadas/genética , Costillas/anomalías , Arritmias Cardíacas/genética , Femenino , Eliminación de Gen , Enfermedades Genéticas Ligadas al Cromosoma X , Gigantismo/genética , Glipicanos/genética , Cardiopatías Congénitas/genética , Humanos , Recién Nacido , Recien Nacido Prematuro , Discapacidad Intelectual/genética , Masculino , LinajeRESUMEN
We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targeted gene panels when testing affected offspring born to consanguineous couples. In this way, exomic data from the parents are also made available for carrier screening, to identify heterozygous pathogenetic and likely pathogenetic variants in genes responsible for other recessive conditions, which may pose a risk for subsequent pregnancies.
Asunto(s)
Adenosina Trifosfatasas/genética , Cadherinas/genética , Lisencefalia/genética , Microcefalia/genética , Polidactilia/genética , Pulgar/anomalías , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Preescolar , Consanguinidad , Exoma/genética , Femenino , Mutación del Sistema de Lectura/genética , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Lactante , Recién Nacido , Lisencefalia/diagnóstico por imagen , Lisencefalia/patología , Microcefalia/diagnóstico por imagen , Microcefalia/patología , Linaje , Fenotipo , Polidactilia/diagnóstico por imagen , Polidactilia/patología , Hermanos , Pulgar/diagnóstico por imagen , Pulgar/patología , Secuenciación del ExomaRESUMEN
Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formylglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C > A; p.S64X and c.818A > G; p.D273G).