Condition

Miller Dieker Syndrome

(MDS)

Isolated Lissencephaly Sequence (ILS)

Subcortical Band Heterotopia (SBH)

Lissencephaly with Cerebellar Hypoplasia (LCH)

Microlissencephaly (MLIS)

Microcephaly with Simplified Gyral Patterns (MSG)

Walker Warburg Syndrome (WWS)

Muscle-Eye_Brain Disease (MEB)

Baraitser Winter Syndrome

(BWS)

Lissencephaly with Abnormal Genitalia (XLAG)

Lissencephaly with agenesis of the corpus callosum (LACC)

Schizencephaly (SCH)

Polymicrogyria

(PMG)

Other names (incl. old Type system)

Classical Lissencephaly

Type I

Classical Lissencephaly

Type I

Classical Lissencephaly

Double Cortex

Subcortical laminar heterotopia

Type I

Classical Lissencephaly

Type I

Radial microbrain, Microcephalia vera, microlissencephaly,

Type IV

Cobblestone

Lissencephaly

Type II

Cobblestone

Lissencephaly

Type II

Classical Lissencephaly

Type I

Berry Kravis syndrome

Distinguishing Features

Low set ears, snub nose, high forehead, indented temples

Some have mild MDS features.

Indented temples

Some have mild MDS features

Extremely small head at birth

Extremely small head at birth

Muscular dystrophy, severe eye abnormalities

Muscular dystrophy, eye abnormalities

eye abnormalities, widely spaced eyes,

droopy eyelids,

broad bridge to nose

Abnormal genitalia

Some have indented temples

Head size

Small

Small

Small

Small

Very small

Very small

Sometimes large with hydrocephalus

Sometimes large with hydrocephalus

Small

Small

Brain appearance

Very smooth all over (agyria)

Thick cortex (10-20mm)

Smooth (agyria/pachygyria)

Moderately thick to thick cortex

Back of brain is smoother than the front with ILS17, front is smoother than the back with ILSX

Visible band below the normal brain cortex

Various -

Some very smooth (agyria)

Some smooth

(agyria/pachygyria)

Some with simple gyri.

Cortex thickness depends on type.

All have abnormal cerebellum

Thick cortex

Simple gyri, shallow sulci

Normal or thin cortex

Cobblestone appearance.

Irregular cortex

Small cerebellum

Cobblestone appearance.

Irregular cortex

Smooth. (agyria/pachygyria) Moderately thick cortex.(5-10mm)

Back of brain is smoother than the front.

Absent corpus callosum

Smooth (agyria/pachygyria), Absent corpus callosum

One or two clefts on the side of the brain

Many small gyri (sometimes this looks like pachygyria on a scan)

All or only parts of the brain may be affected

Sub types of condition

None

ILS17, ILSX &

ILS (cause unknown)

SBHX, SBH17

6 different types identified LCHa to LCHf

3 different types identified, MLIS1 to MLIS3

MSG1, MSG2, MSG3, MSG4 and MSG5

None

None

None

None

None

7 different types identified, BDP, BGP, BPP/CBPS, BPOP, BFP, BMOP, PMG-WM

Cause

Deletion  on chromosome 17

involving LIS1 and 14-3-3e gene

Either

·          Small deletion on chromosome 17 involving LIS1 gene or

·          Mutations in LIS1 gene   or

·          DCX gene – X linked   (boys only) or

·          Other - unknown

Mutation in either

·          LIS1 gene (mosaicism)

·          DCX gene (X linked)

·          Other -unknown

LCHa

Mutations in

·          LIS1 gene or

·          DCX gene (X linked)

·          Other –unknown

LCHb

·          RELN gene

Many probably genetic – gene(s) unknown

Many probably genetic – gene(s) unknown

Mutation in POMT1 gene located on chromosome 9 in 20% of cases

Mutation in MEB gene (POMGnT1) located on chromosome 1

Genetic  – gene(s) unknown

Mutation in  ARX gene on X chromosome

Genetic  – gene(s) unknown

Some are genetic, some are due to CMV infection

Either genetic or can be caused by other intrauterine problems

Inherited?

In approx.  12% of cases one parent is a carrier,

of a predisposing

chromosome

rearrangement (translocation)

The X-linked version can be inherited from a carrier mother

The X-linked version can be inherited from a carrier mother

X-linked version can be inherited from a carrier mother

In other types of LCH (b–f), both parents are thought to be a carriers

Inheritance commonly compatible with both parents being carriers

(Recessive pattern)

Inheritance commonly compatible with both parents being carriers

(Recessive pattern)

Yes, both parents are carriers.  (Recessive pattern)

Yes, both parents are carriers.  (Recessive pattern)

Rarely both parents are carriers.  (Recessive pattern)

can be inherited from a carrier mother?????

Inheritance commonly compatible with both parents being carriers

(Recessive pattern)

Generally not

All inheritance patterns have been noted

Recurrence in other children

Approx 30% where one parent is a carrier.

Very low otherwise.

Very low unless mother is carrier of X linked version in which case the recurrence is 50% (as both

girls and boys can be

affected with SBH  or  ILSX)

Very low unless mother is carrier of X linked version in which case the recurrence is 50% (as both girls and boys can be affected with SBH or  ILSX)

For LIS1 very low.

If mother is carrier of X linked version, the recurrence is 50% (as both girls and boys can be affected with SBH or  LIS)

For others 25%

as high as 25%

as high as 25%

25%

25%

as high as 25%, but generally low

recurrence is 50% if mother is a carrier

as high as 25%

low

May be as high as 50% but also may be very low