Face and Head Abnormality

Leukodystrophy can affect physical appearance. The facial features described here occur in several leukodystrophies. Not all will directly affect health, but facial abnormalities can have psychological consequences, either for the affected individual or for family members looking after them. Connecting with others who are coping with these and other symptoms can be a great comfort,
as can mental health support.

Head Size

Abnormalities in head size are quite common in leukodystrophies. Smaller than normal head size is called microcephaly and larger than normal is called macrocephaly.

• Microcephaly can be present at birth or can develop within the first few years of life. It occurs when the brain has stopped growing or has not developed properly. Microcephaly can be linked to cognitive issues, seizures and developmental delay. There is no treatment for microcephaly itself. Treatment focuses on reducing the impact of any cognitive and developmental difficulties the child has, and controlling seizures.

o Leukodystrophies that may have microcephaly as a symptom include Aicardi-Goutieres Syndrome, Cockayne Syndrome; 3-Methylglutaconic Aciduria type 1; Methylenetetrahydrofolate Reductase Deficiency; Oculodentodigital Dysplasia with cerebral white matter abnormalities; Pelizaeus-Merzbacher-Like Disease; RARS-related hypomyelination.

• Macrocephaly can also be linked to cognitive disability and delay, although some children with macrocephaly have no other symptoms. Rapid head growth may occur alongside slow growth of the rest of the body. Those with macrocephaly often have hydrocephalus, which is a build-up of cerebrospinal fluid in the brain. Treatment of macrocephaly focuses on managing any underlying causes, such as hydrocephalus, and reducing the impact of cognitive and developmental issues. Hydrocephalus can often be treated by inserting a tube and catheter (called a ‘shunt system’) to allow fluid to flow away from the brain.

o People with the following conditions may be affected by macrocephaly: Alpha-Mannosidosis; Alexander Disease (type 1); Canavan Disease; Glutaric Acidemia type 1; L-2-hydroxyglutaric aciduria.

o GM2 gangliosidosis and Megalencephalic Leukodystrophy with subcortical Cysts can have megalencephaly as a symptom. Megalencephaly is macrocephaly caused by an abnormally large brain. Again, treatment focuses on reducing the impact of cognitive and developmental issues and seizures: there is no cure for megalencephaly.

• Large fontanelles are a symptom of some leukodystrophies (D-Bifunctional Protein Deficiency; Glutaric Acidemia type 1; Zellweger Syndrome). Fontanelles are ‘soft spots’ on an infant’s head, caused by gaps in the bones of the skull. All infants have these for the first few months of life to allow brain growth and development, before the bones close. In some cases, large fontanelles may be due to hydrocephalus (abnormal levels of cerebrospinal fluid in the brain). Large fontanelles may take longer than normal to close.


A protruding upper or lower jawbone, known as prognathism, is a symptom of two leukodystrophies (Alpha-Mannosidosis; Cockayne Syndrome). Corrective jaw surgery is unlikely to be considered appropriate for those with a leukodystrophy.

Other conditions are affected by retrognathism, in which the jawbone is set back (D-Bifunctional Protein Deficiency). Retrognathism can affect an individual’s ability to chew food, and may also affect ability to breathe, especially when asleep. They may experience sleep apnoea, in which breathing stops for several seconds while sleeping. Surgery may be available for retrognathism if it is causing these problems.

A small jawbone, or micrognathism, can affect those with Sialic Acid Storage Disorders. It may cause feeding problems, and is also treatable with corrective surgery if appropriate.

Jaw conditions can affect dental development. Problems such as misalignment of the teeth can cause difficulties with chewing, biting and talking and an increased risk of tooth decay and gum disease.

Dental Issues

People with leukodystrophy may experience a range of dental problems. Some are caused by jaw abnormalities, as described above. Another condition is hypodontia (under-developed or missing teeth). This can occur in people with POLR1C-related leukodystrophy and Oculodentodigital Dysplasia with cerebral white matter abnormalities in particular. People with POLR3-related leukodystrophy may also have abnormal teeth.

• Any dental issues may affect an individual’s ability to talk, bite or chew. Dental surgery – including braces and tooth replacement with fillings, dentures or bridges – can help people with hypodontia by improving pronunciation and chewing ability.

• Dental problems can also cause pain. To avoid this, people with leukodystrophies should have regular dental appointments as far as is possible. See our Dental section in Condition Management.

Other facial abnormalities

Some leukodystrophies are associated with distinctive facial features. These can include a high, wide or protruding forehead, a flattened nasal bridge and broad nose, and large misshapen and/or low set ears. An unusually thin nose can also be a distinctive feature. Eyes may be sunken, far apart (hypertelorism) or notably small (microphthalmia), or eyelid closure may be poor. A small number of conditions are associated with cleft lip or cleft palate. For those with Fucosidosis, thickened lips and tongue may be evident. People with Sialic acid storage disorders may have anteverted (upturned) nostrils.

Conditions that may be affected by facial abnormalities include:

Cockayne Syndrome
D-Bifunctional Protein Deficiency
Glutaric Acidemia type 1
Infantile Refsum’s Disease
Neonatal Adrenoleukodystrophy
Oculodentodigital Dysplasia with cerebral white matter abnormalities

Peroxisomal Acyl-CoA Oxidase Deficiency
Sialic Acid Storage Disorders
Zellweger Syndrome

Please see individual condition pages for more specific information.