Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies syndrome

What it is

From: Orphanet

A rare disorder of ornithine metabolism characterized by global developmental delay, alopecia, macrocephaly, and dysmorphic facial features (including high and broad forehead, hypertelorism, ptosis, blepharophimosis, downslanting palpebral fissures, deep-set eyes, large ears, and retrognathia or high arched palate). Additional reported manifestations are sensorineural hearing loss, spasticity, hypotonia, hypoplastic nails, cryptorchidism, and clinodactyly, among others. Brain imaging may show white matter abnormalities, periventricular cysts, enlarged lateral ventricles, or prominent perivascular spaces.

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 eyebrow · Frequent (79-30%)

Absence of the eyebrow.

Aggressive behavior · Frequent (79-30%)

Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).

Attention deficit hyperactivity disorder · Frequent (79-30%)

Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient.

Bilateral cryptorchidism · Frequent (79-30%)

Absence of both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum.

Bulbous nose · Frequent (79-30%)

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

Deeply set eye · Frequent (79-30%)

An eye that is more deeply recessed into the plane of the face than is typical.

Dilation of Virchow-Robin spaces · Frequent (79-30%)

Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery.

Global developmental delay · Frequent (79-30%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

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.

Hypertelorism · Frequent (79-30%)

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Large for gestational age · Frequent (79-30%)

The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.

Macrocephaly · Frequent (79-30%)

Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Macrotia · Frequent (79-30%)

Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).

Neonatal hypotonia · Frequent (79-30%)

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

Other findings in the same source

From: Orphanet

Additional reported features include Polyhydramnios (Frequent (79-30%)); Small nail (Frequent (79-30%)); Sparse eyelashes (Frequent (79-30%)); Bilateral ptosis (Frequent (79-30%)); Large forehead (Frequent (79-30%)); Abnormality of the cerebellar vermis (Occasional (29-5%)); Absent eyelashes (Occasional (29-5%)); Absent speech (Occasional (29-5%)); Alopecia (Occasional (29-5%)); Asthma (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Antenatal; Neonatal

Inheritance in the source

From: Orphanet

Autosomal dominant

Frequency and the population described

From: Orphanet

Reported case(s): 5.0; 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 dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies syndrome is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

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.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies 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.