[7][12] Among a number of adverse neurological effects sometimes found with an absence of the corpus callosum, intellectual disability has been shown to occur at a rate of approximately 73 percent.

[7][13][18] While psychiatric conditions like these are to be expected with LFS, there have also been cases of the disorder with some preservation of mental and behavioral abilities, such as problem solving, reasoning and normal intelligence.

[2] Craniofacial and other features of LFS include: maxillary hypoplasia (underdevelopment of the upper jaw bone),[9] a small mandible (lower jaw bone) and receding chin,[3][17] a high-arched palate (the roof of the mouth), with crowding and misalignment of the upper teeth;[5][7] macrocephaly (enlarged skull) with a prominent forehead,[3][9] hypernasal speech (voice),[5][7] a long nose with a high, narrow nasal bridge;[9] a deep, short philtrum (the indentation in the upper lip, beneath the nose),[9] low-set ears with some apparent retroversion,[9] hypotonia (decreased muscle tone),[3] pectus excavatum (a malformity of the chest),[9] slightly enlarged to normal testicular size in males,[9][17] and seizures.

[13][25] A number of features involving the heart have been noted in several LFS cases, the most significant being dilation of the aortic root, a section of the ascending aorta.

[26] As this presents a possible life-threatening consequence of LFS, routine cardiac evaluation methods such as echocardiogram are implemented when the disorder is first diagnosed, along with MRI scans of the brain to screen for suspected agenesis of the corpus callosum.

Marfanoid habitus, a highly arched palate and several other features of LFS can be found with Marfan syndrome, a connective tissue disorder.

[4] The finding of aortic root dilation in both disorders suggests that a mutation in an unspecified connective tissue regulating gene may contribute to the etiology of LFS.

[13][37] A scenario such as this would also be possible with X-linked recessive inheritance, but in this particular case report, the girl was believed to be a manifesting heterozygote[13][37] carrying one copy of the mutated gene.

Sporadic cases of LFS, where the disorder is present in an individual with no prior family history of it, have also been reported in a small number of affected males.

[13][15][38] An individual exhibiting intellectual disability and other symptoms similar to LFS was found to have a terminal deletion of the subtelomeric region in the short arm of chromosome 5.

[25] Deletion of this area of chromosome 5 is associated with intellectual disability, psychotic behavior, autism, macrocephaly and hypernasal-like speech, as well as the disorder Cri du chat syndrome.

[41] Mutations in UPF3B alter and prevent normal function of the NMD pathway, resulting in translation and expression of truncated mRNA sequences into malfunctioning proteins that can be associated with developmental errors and intellectual disability.

[3][43] Common features shared by both LFS and FGS include X-linked intellectual disability, hyperactivity, macrocephaly, corpus callosum agenesis and hypotonia.

[3][46] As both disorders originate from an identical type of mutation in the same gene, while exhibiting similar, yet distinct characteristics; LFS and FGS are considered to be allelic.

[21] The initial observation of suspected X-linked intellectual disability with Marfanoid features and craniofacial effects such as a high-arched palate was described by Lujan et al. in 1984.

[3][13][17] Additional investigations of combined X-linked intellectual disability and Marfanoid habitus in other families, including two brothers, were reported by Fryns et al., beginning in 1987.