Lambotte syndrome: Microcephaly, holoprosencephaly, intrauterine growth retardation, facial anomalies, and early lethality—A new sublethal multiple congenital anomaly/mental retardation syndrome in four sibs

Abstract

We report on an Arabic sibship originating from Morocco in which four children manifest an undiagnosed sublethal multiple congenital anomaly/mental retardation (MCA/MR) syndrome of intrauterine growth retardation (IUGR), microcephaly, large soft pinnae, telecanthus or true hypertelorism with squint, flat face, unusual hooked nose, very narrow mouth, retrognathia, and extremely severe neurologic impairment. One child was stillborn. Three others died in a cachectic state during their second year. One child had a severe cerebral malformation compatible with semilobar holoprosencephaly. Other inconstant manifestations are anterior chamber cleavage defect, preaxial polydactyly of feet, interventricular septal defect, and atresia of the external auditory meatus. Autosomal recessive inheritance is likely.

Submicroscopic terminal deletions and duplications in retarded patients with unclassified malformation syndromes

“…Some of those cases were previously published and accepted as bona fide Mendelian phenotypes: Lambotte syndrome (case 10; Verloes et al 1990;Herens et al 1997), GOMBO syndrome (case 11; Verloes et al 1989Verloes et al , 2000 or Haspeslagh syndrome (Haspelslagh et al 1985;Devriendt et al 2000). Screening for telomeres in patients with de novo visible aberrations was also shown to detect familial rearrangements and more precisely define de novo aberrations: Kashork et al (1999), studying 32 patients with a visible "de novo" del(1p36), showed that the apparently terminal 1p deletion resulted from a cryptic rearrangement in five cases (three with 1qter; each one with 2pter and Xpter) and was an interstitial deletion in five other cases.…”

“…A reciprocal rearrangement was observed at prenatal diagnosis in a further family member. The family was initially reported as having an autosomal recessive malformation syndrome (Verloes et al 1990). The discovery of the familial unbalanced rearrangement lead to an update (Herens et al 1997).…”

Telomeres: a diagnosis at the end of the chromosomes

“…Prenatal diagnosis of a fetus with a cryptic t(4;18)(p15.32;p11.21) was reported by Kohlschmidt et al 48 The Lambotte syndrome (microcephaly, holoprosencephaly, intrauterine growth retardation, facial anomalies, and early lethality) initially reported as an autosomal recessive disorder 49 was found to be caused by a deletion of 4p16.2-pter and a duplication of 2q37.1-qter.…”

Cerebral malformation, seizures, hypertrichosis, distinct face, claw hands, and overlapping fingers in sibs of both sexes

“…Another malformation pattern with cerebral malformations, hypertelorism, unusual face, neurological anomalies, and early death was described by Verloes et al [1990] in the Lambotte syndrome. In contrast to this disorder our patients were initially macrocephalic with lack of postnatal head growth and premature fusion of sutures.…”