TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome

What it is

From: Orphanet

A rare multiple congenital anomalies/dysmorphic syndrome characterized by profound intellectual disability with absent speech, severe infantile hypotonia with decreased or absent reflexes, markedly slow motor development (with no progress beyond the ability to sit independently), early-onset epilepsy, strabismus and post-natal onset of progressive brain atrophy (including loss of brain volume, ex vacuo ventriculomegaly, dysgenesis of corpus callosum, white matter abnormalities ranging from non-specific changes to leukodystrophy). Swallowing difficulties, respiratory insufficiency, osteoporosis and variable craniofacial dysmorphisms (including plagio/brachycephaly, bitemporal narrowing, high-arched eyebrows high nasal bridge, anteverted nares, high palate, tented upper lip) may constitute additional clinical features.

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.

EMG: chronic denervation signs · Very frequent (99-80%)

Evidence of chronic denervation on electromyography.

Neonatal hypotonia · Very frequent (99-80%)

Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.

Severe muscular hypotonia · Very frequent (99-80%)

A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.

Progressive muscle weakness · Very frequent (99-80%)

Abnormal circulating lipid concentration · Frequent (79-30%)

Any deviation from the normal concentration of lipid in the blood circulation.

Abnormal facial shape · Frequent (79-30%)

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

Abnormal periventricular white matter morphology · Frequent (79-30%)

A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles.

Areflexia · Frequent (79-30%)

Absence of neurologic reflexes such as the knee-jerk reaction.

Coarse facial features · Frequent (79-30%)

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Delayed speech and language development · Frequent (79-30%)

A degree of language development that is significantly below the norm for a child of a specified age.

Global brain atrophy · Frequent (79-30%)

Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size.

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

Underdevelopment of the corpus callosum.

Inability to walk · Frequent (79-30%)

Incapability to ambulate.

Multifocal seizures · Frequent (79-30%)

Seizures that start from several different areas of the brain (i.e., with multiple ictal onset locations).

Other findings in the same source

From: Orphanet

Additional reported features include Reduced tendon reflexes (Frequent (79-30%)); Seizure (Frequent (79-30%)); Severe global developmental delay (Frequent (79-30%)); Skeletal muscle atrophy (Frequent (79-30%)); Ventriculomegaly (Frequent (79-30%)); Respiratory insufficiency (Frequent (79-30%)); Broad forehead (Occasional (29-5%)); Bulbous nose (Occasional (29-5%)); Cognitive impairment (Occasional (29-5%)); Delayed skeletal maturation (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 25.0; 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 TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome 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 TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome. 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.