Fronto-otopalatodigital osteodysplasia: Clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalatodigital syndrome types 1 and 2, and frontometaphyseal dysplasia

Abstract

Otopalatodigital syndrome type 2 is an X-linked disorder with minimal expression in carrier females and comprises typical facial anomalies and a generalized bone dysplasia with osteodysplastic changes, brachydactyly, and impaired survival. Recently several other severe malformations were reported in the condition. Melnick-Needles syndrome is an X-linked dominant disorder. Affected males are usually sporadic cases. The exceptional males born to symptomatic women present with a lethal disorder comprising generalized osteodysplasia, deficiency of the first ray, and facial anomalies strikingly similar to those of otopalatodigital syndrome type 2. We report here on three boys with classical, severe, and lethal otopalatodigital type 2 syndrome, and three boys with severe (lethal) Melnick-Needles syndrome, born to affected mothers. We suggest that otopalatodigital type 1 and 2, Melnick-Needles syndrome and frontometaphyseal dysplasia, sharing many clinical manifestations and a similar mode of inheritance, are variants of the same condition: fronto-otopalatodigital osteodysplasia. The relationships to similar syndromes (i.e., Saint-Martin-Gardner-Morrisson syndrome, serpentine fibula syndrome, atelosteogenesis type 3, boomerang dysplasia, and Yunis-Varon syndrome) are discussed.

Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans

“…1 online), segregate with the disease phenotype in a total of 59 meioses (data not shown) and were not observed in at least 100 control chromosomes. We conclude that OPD1, OPD2, FMD and MNS are allelic conditions 12 , which we collectively term 'OPD-spectrum disorders' . All (17 of 17) mutations reported here, in contrast with a small minority (2 of 14) associated with PVNH 3,5,6 , conserve the reading frame and are predicted to produce full-length filamin A.…”

Síndrome otopalatodigital tipo II, aproximación prenatal y diagnóstico clínico de un caso complejo de displasia ósea

“…El fallecimiento suele ser perinatal, algunos pacientes solo alcanzan pocos meses de vida (1,2,3). Recientemente se ha demostrado que los pacientes con OPD 2 tienen mutaciones en el gen A filamina (FLNA), que también se encuentra alterado en entidades alélicas como el síndrome de OPD1, el síndrome Melnik-Needles, y displasia frontometafisaria (2)(3)(4)(5). Robertson en 2005 (5), propuso el término osteodisplasia fronto-oto-palato-digital para agrupar estas cuatro entidades que tiene características fenotípicas comunes y el mismo gen alterado.…”

A Japanese case of oto-palato-digital syndrome type II: an apparent lack of phenotype–genotype correlation

“…OPD syndrome is classified into two types according to clinical severity: the mild form OPD I (OMIM: 311300), and the severe form OPD II (OMIM: 304120; Taybi 1962;Dudding et al 1967;Fitch et al 1976Fitch et al , 1983Brewster et al 1985). Furthermore, several patients have been reported to have overlapping clinical features among OPD I and II, Larsen syndrome, atelosteogenesis I and II, boomerang dysplasia, the lethal male Melnick-Needles syndrome, and acro-coxo-melic dysplasia (Plauchu et al 1984;Blanchet et al 1993;Nishimura et al 1997;Robertson et al 1997;Verloes et al 2000).…”