PYCR2-related microcephaly-progressive leukoencephalopathy

What it is

From: Orphanet

PYCR2-related microcephaly-progressive leukoencephalopathy is a rare, genetic, syndromic intellectual disability disorder characterized by progressive postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial hypotonia, appendicular hypertonia with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and failure to thrive. Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Absent speech · Very frequent (99-80%)

Complete lack of development of speech and language abilities.

Failure to thrive · Very frequent (99-80%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Feeding difficulties · Very frequent (99-80%)

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Inability to walk · Very frequent (99-80%)

Incapability to ambulate.

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Progressive microcephaly · Very frequent (99-80%)

Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.

Severe global developmental delay · Very frequent (99-80%)

A severe delay in the achievement of motor or mental milestones in the domains of development of a child.

Abnormal facial shape · Frequent (79-30%)

An abnormal morphology (form) of the face or its components.

Bulbous nose · Frequent (79-30%)

Increased volume and globular shape of the anteroinferior aspect of the nose.

CNS hypomyelination · Frequent (79-30%)

Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.

Developmental regression · Frequent (79-30%)

Loss of developmental skills, as manifested by loss of developmental milestones.

Hyperintensity of cerebral white matter on MRI · Frequent (79-30%)

A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.

Hypoplasia of the corpus callosum · Frequent (79-30%)

Underdevelopment of the corpus callosum.

Hypoplasia of the maxilla · Frequent (79-30%)

Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.

Other findings in the same source

From: Orphanet

Additional reported features include Hypotonia (Frequent (79-30%)); Low-set ears (Frequent (79-30%)); Protruding ear (Frequent (79-30%)); Seizure (Frequent (79-30%)); Severe demyelination of the white matter (Frequent (79-30%)); Skeletal muscle atrophy (Frequent (79-30%)); Spasticity (Frequent (79-30%)); Vomiting (Frequent (79-30%)); Abnormality of the skeletal system (Occasional (29-5%)); Agenesis of corpus callosum (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 18.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing PYCR2-related microcephaly-progressive leukoencephalopathy is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

Additional services that may be relevant, depending on the findings, include: Neurology.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for PYCR2-related microcephaly-progressive leukoencephalopathy. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.