Microcephalic cortical malformations-short stature due to RTTN deficiency

What it is

From: Orphanet

A rare, genetic, neurodevelopmental disorder with primordial microcephaly characterized by primary microcephaly, moderate to severe intellectual disability, and global developmental delay. Variable brain malformations are common ranging from simplified gyration, to cortical malformations such as pachygyria, polymicrogyria, reduced sulcation and midline defects. Craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) are related to the primary microcephaly. Short stature is frequently observed, and may be severe.

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.

Abnormal facial shape · Very frequent (99-80%)

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

Microcephaly · Very frequent (99-80%)

Head circumference below 2 standard deviations below the mean for age and gender.

Intellectual disability, severe · Frequent (79-30%)

Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34.

Intrauterine growth retardation · Frequent (79-30%)

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Polymicrogyria · Frequent (79-30%)

Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).

Severe global developmental delay · Frequent (79-30%)

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

Severe short stature · Frequent (79-30%)

A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.

Sloping forehead · Frequent (79-30%)

Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.

Ventriculomegaly · Frequent (79-30%)

An increase in size of the ventricular system of the brain.

Multiple joint contractures · Frequent (79-30%)

Poor speech · Frequent (79-30%)

Severe failure to thrive · Frequent (79-30%)

2-5 finger cutaneous syndactyly · Occasional (29-5%)

A soft tissue continuity in the anteroposterior axis between the second to the fifth fingers that extends distally to at least the level of the proximal interphalangeal joints.

4-5 finger syndactyly · Occasional (29-5%)

A soft tissue continuity in the anteroposterior axis between the fourth (ring) to the fifth (little) finger that extends distally to at least the level of the proximal interphalangeal joints.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormal periventricular white matter morphology (Occasional (29-5%)); Abnormal pyramidal sign (Occasional (29-5%)); Abnormal renal collecting system morphology (Occasional (29-5%)); Abnormal repetitive mannerisms (Occasional (29-5%)); Abnormality of the occipital bone (Occasional (29-5%)); Agenesis of corpus callosum (Occasional (29-5%)); Arachnoid cyst (Occasional (29-5%)); Attenuation of retinal blood vessels (Occasional (29-5%)); Axial hypotonia (Occasional (29-5%)); Bilateral microphthalmos (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): 28.0; 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 Microcephalic cortical malformations-short stature due to RTTN deficiency is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

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

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.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Microcephalic cortical malformations-short stature due to RTTN deficiency. 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.