Malan syndrome

[MIM 614 753]

(sometimes known as Sotos type 2 syndrome)

Prevalence < 1/1.106. Sporadic. Mutation (microdeletion or variant) of the NFIX (nuclear factor I X) gene (19p13.3): other mutations of this gene can lead to Marshall-Smith syndrome (see this term). Overgrowth syndrome close to Sotos syndrome (see this term)


Association of:

-        moderate excessive postnatal growth (up to 2 SD for age)

-        macrocephaly (75 %), (up to 2.3 SD for age)

-        craniofacial dysmorphism: long or triangular face, prominent forehead, high implantation of hair, downslanting palpebral fissures, short nose with upturned tip, long philtrum, prominent chin, everted lower lip, retrognathia, low-set ears, preauricular appendices

-        hypotonia

-        advanced bone age

-        developmental retardation and intellectual deficit.

    Sometimes:

-        behavioral disorder (anxiety, extreme sensitivity to noise) with or without autistic traits,

-        eye abnormalities: strabismus (65 %), nystagmus, paleness/hypoplasia of the optic disc (25 %),

-        gastrointestinal problems: vomiting, chronic diarrhea, constipation,

-        scoliosis, pectus excavatum (40 %) or carinatum

-        long fingers (hands/feet)

-        body hemihypertrophy

-        vascular abnormalities

-        slightly enlarged cerebral ventricles.

-        progressive dilation of the ascending aorta


In case of an associated deletion of the CACNA1A gene (19p13.2) (contiguous gene disorder), cerebellar ataxia, epilepsy and migraines can be present.


Anesthetic implications:

intellectual deficit, very anxious patient, risk of difficult intubation


References :

-        Klaassens M, Morrogh D, Rossen EM, Jaffer F et al.
Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and review of the literature.
Eur J Med Genet 2015; 23: 610-5.

-        Priolo M, Schanze D, Tatton-Brown K, Mulder PA et al.
Further delineation of Malan syndrome.
Human Mutations 2018; 39: 126-37.

-        Partyka LM.
Anesthetic considerations in an infant with Malan syndrome: a case report.
A&A Practice 2022; 16e01600


Updated: July 2022