Malan syndrome (MIM# 614753; also known as Sotos syndrome 2) is a disorder characterized by postnatal overgrowth,
macrocephaly, advanced bone age, long narrow face, high forehead, and intellectual
disability. It results from heterozygous variants or microdeletions of nuclear factor
I/X (NFIX; MIM# 164005) on chromosome 19p13.2 [
[1]
]. Although distinguishing Malan syndrome from two similar overgrowth disorders—Sotos
(MIM# 117550) and Weaver syndromes (MIM# 277590)—is possible by clinical evaluation [
- Priolo M.
- Schanze D.
- Tatton-Brown K.
- Mulder P.A.
- Tenorio J.
- Kooblall K.
- Acero I.H.
- Alkuraya F.S.
- Arias P.
- Bernardini L.
- Bijlsma E.K.
- Cole T.
- Coubes C.
- Dapia I.
- Davies S.
- Di Donato N.
- Elcioglu N.H.
- Fahrner J.A.
- Foster A.
- Gonzalez N.G.
- Huber I.
- Iascone M.
- Kaiser A.S.
- Kamath A.
- Liebelt J.
- Lynch S.A.
- Maas S.M.
- Mammi C.
- Mathijssen I.B.
- McKee S.
- Menke L.A.
- Mirzaa G.M.
- Montgomery T.
- Neubauer D.
- Neumann T.E.
- Pintomalli L.
- Pisanti M.A.
- Plomp A.S.
- Price S.
- Salter C.
- Santos-Simarro F.
- Sarda P.
- Segovia M.
- Shaw-Smith C.
- Smithson S.
- Suri M.
- Valdez R.M.
- Van Haeringen A.
- Van Hagen J.M.
- Zollino M.
- Lapunzina P.
- Thakker R.V.
- Zenker M.
- Hennekam R.C.
Further delineation of Malan syndrome.
[1]
], these are symptomatically similar and share several clinical features. Shimojima
et al. [
- Priolo M.
- Schanze D.
- Tatton-Brown K.
- Mulder P.A.
- Tenorio J.
- Kooblall K.
- Acero I.H.
- Alkuraya F.S.
- Arias P.
- Bernardini L.
- Bijlsma E.K.
- Cole T.
- Coubes C.
- Dapia I.
- Davies S.
- Di Donato N.
- Elcioglu N.H.
- Fahrner J.A.
- Foster A.
- Gonzalez N.G.
- Huber I.
- Iascone M.
- Kaiser A.S.
- Kamath A.
- Liebelt J.
- Lynch S.A.
- Maas S.M.
- Mammi C.
- Mathijssen I.B.
- McKee S.
- Menke L.A.
- Mirzaa G.M.
- Montgomery T.
- Neubauer D.
- Neumann T.E.
- Pintomalli L.
- Pisanti M.A.
- Plomp A.S.
- Price S.
- Salter C.
- Santos-Simarro F.
- Sarda P.
- Segovia M.
- Shaw-Smith C.
- Smithson S.
- Suri M.
- Valdez R.M.
- Van Haeringen A.
- Van Hagen J.M.
- Zollino M.
- Lapunzina P.
- Thakker R.V.
- Zenker M.
- Hennekam R.C.
Further delineation of Malan syndrome.
[2]
] identified three patients with Malan syndrome due to 19p13.2 microdeletion as having
Chiari malformation type I (CMI), including two of their own patients and one reported
by Dolan et al. [
[3]
] and stated that the incidence of CMI in patients with 19p13.2 deletions involving
NFIX is 15.8% [
[2]
]. The authors speculated that NFIX or its neighboring genes may be associated with CMI and suggested that the presence
of CMI may help differentiate 19p13.2 deletion syndrome from the NSD1-related Sotos syndrome. Following this study, a large cohort of Malan syndrome patients
with NFIX mutations was reported and three of 44 cases showed Chiari malformation by imaging
studies [
[1]
]. However, the underlying mechanism by which CMI develops in Malan syndrome patients
remains uncertain. Here we report a novel NFIX variant in a subject with Malan syndrome accompanying hindbrain overcrowding reminiscent
of CMI.- Priolo M.
- Schanze D.
- Tatton-Brown K.
- Mulder P.A.
- Tenorio J.
- Kooblall K.
- Acero I.H.
- Alkuraya F.S.
- Arias P.
- Bernardini L.
- Bijlsma E.K.
- Cole T.
- Coubes C.
- Dapia I.
- Davies S.
- Di Donato N.
- Elcioglu N.H.
- Fahrner J.A.
- Foster A.
- Gonzalez N.G.
- Huber I.
- Iascone M.
- Kaiser A.S.
- Kamath A.
- Liebelt J.
- Lynch S.A.
- Maas S.M.
- Mammi C.
- Mathijssen I.B.
- McKee S.
- Menke L.A.
- Mirzaa G.M.
- Montgomery T.
- Neubauer D.
- Neumann T.E.
- Pintomalli L.
- Pisanti M.A.
- Plomp A.S.
- Price S.
- Salter C.
- Santos-Simarro F.
- Sarda P.
- Segovia M.
- Shaw-Smith C.
- Smithson S.
- Suri M.
- Valdez R.M.
- Van Haeringen A.
- Van Hagen J.M.
- Zollino M.
- Lapunzina P.
- Thakker R.V.
- Zenker M.
- Hennekam R.C.
Further delineation of Malan syndrome.
Keywords
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Article Info
Publication History
Published online: February 22, 2020
Accepted:
February 21,
2020
Received in revised form:
February 19,
2020
Received:
December 13,
2019
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
