Phenotype and natural history in Marshall–Smith syndrome

Abstract

Marshall–Smith syndrome (MSS) is a distinctive entity of unknown etiology with fewer than 50 patients described in the medical literature to date. Through an International collaboration and use of an online wiki to facilitate data collection and sharing, we further delineate the phenotype and natural history of this syndrome. We present 15 new patients, the oldest being 30 years, provide an update on four previously published cases, and compare all patients with other patients reported in literature. Main clinical features are moderate to severe developmental delay with absent or limited speech, unusual behavior, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Facial features are characteristic with high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor abnormalities of brain morphology such as hypoplasia of the corpus callosum are common. Mortality from respiratory complications is high, but airway support increasingly allows survival into adulthood. Array‐CGH was performed on 12 of the cohort and no copy number variants of clear clinical relevance were identified. The present study is the first reported use of an online wiki to aid delineation of a genetic syndrome, and illustrates its value in collecting detailed data in rare conditions. © 2010 Wiley‐Liss, Inc.

Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features

“…Although both syndromes has high forehead, Sotos syndrome has a long/narrow face, triangular shaped face with a prominent chin, down-slanting of the palpebral fissures, 1,4-5 whereas Marshall-Smith syndrome has proptosis, underdeveloped midface and prominent premaxilla. 7,14 In patient 1, although some characteristic features of Marshall-Smith syndrome such as everted lower lip, short nose and midface hypoplasia were observed, overall facial appearance, overgrowth features at 17 month of age, scoliosis, hypotonia and seizures were consistent with Sotos syndrome. Similarly, in patient 2, the facial appearance, tall stature and macrocephaly were consistent with Sotos syndrome.…”

“…5 On the other hand, main clinical features of Marshall-Smith syndrome are moderate to severe developmental delay with absent or limited speech, unusual behavior, disharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature and kyphoscoliosis. 14 One of remarkable differences between Sotos syndrome and MarshallSmith syndrome is facial appearances. Although both syndromes has high forehead, Sotos syndrome has a long/narrow face, triangular shaped face with a prominent chin, down-slanting of the palpebral fissures, 1,4-5 whereas Marshall-Smith syndrome has proptosis, underdeveloped midface and prominent premaxilla.…”

Beckwith–Wiedemann syndrome and Chiari I malformation—a case-based review of central nervous system involvement in hemihypertrophy syndromes

“…Congenital hypertrophy itself is known to either occur in isolation or in conjunction with these syndromes such as Proteus, Sotos, Klippel-TrenaunayWeber, Weaver, Marshal-Smith, Costello, and SimpsonGolabi-Behmel syndromes [6,8,9,11,12,14,18,20,21,24,26,27,29,31] (Table 1). Congenital hypertrophy is classified as simple when only a single extremity is involved, complex when majority of one half of the body is affected, with involvement of either the same side or both sides, and hemifacial when it involves only one side of the face [26].…”

Sindrome de Marshall- Smith en mujer adulta. Nuevos retos en anticoncepción

“…El síndrome de Marshall Smith es una enfermedad genética incluida en el registro de enfermedades raras, con una incidencia no bien establecida, pero inferior a 1/100000, y con menos de 50 casos descritos hasta la fecha en la literatura médica 1 . De etiología desconocida, se han descrito mutaciones "de novo" en los exones 2 y 6-10 del gen NFIX 2 .…”

“…De etiología desconocida, se han descrito mutaciones "de novo" en los exones 2 y 6-10 del gen NFIX 2 . Fue descrita por primera vez en 1971 3 y cursa con una maduración ósea acelerada, rasgos dismórficos (frente prominente, macizo facial pequeño, ojos prominentes, escleróticas azules, narinas antevertidas, puente nasal plano, micrognatia, labios evertidos), alteraciones cerebrales (hipoplasia del cuerpo calloso) 2,5,7,8 , baja talla, cifoescoliosis 8 , defectos cutáneos en la pigmentación 9 , pubertad precoz central y rodete subaórtico 10 , y en ocasiones alteraciones en el desarrollo neuropsicomotor 3,4,7 . El compromiso respiratorio por obstrucción de las vías altas es la patología principal que produce infecciones respiratorias de repetición, condiciona un déficit de crecimiento y disminuye las posibilidades de supervivencia hasta la etapa adulta 5,7 incluyendo un alto riesgo de sufrir complicaciones anestésicas en relación con el mantenimiento de las vías aéreas 6 .…”