Schinzel-Giedion syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Schinzel-Giedion syndrome is a severe condition that is apparent at birth and affects many body systems. Signs and symptoms of this condition include distinctive facial features, neurological problems, and organ and bone abnormalities. Because of their serious health problems, most affected individuals do not survive past childhood.

Children with Schinzel-Giedion syndrome can have a variety of distinctive features. In most affected individuals, the middle of the face looks as though it has been drawn inward (midface retraction). Other facial features include a large or bulging forehead; wide-set eyes (ocular hypertelorism); a short, upturned nose; and a wide mouth with a large tongue (macroglossia). Affected individuals can have other distinctive features, including larger than normal gaps between the bones of the skull in infants (fontanelles), a short neck, low-set ears, and an inability to secrete tears (alacrima). Babies with Schinzel-Giedion syndrome often have excessive hairiness (hypertrichosis) that usually disappears in infancy.

Children with Schinzel-Giedion syndrome have severe developmental delay. Other neurological problems can include severe feeding problems, seizures, or visual or hearing impairment. They may also experience short pauses in breathing during sleep (sleep apnea).

Affected individuals can also have abnormalities of organs such as the heart, kidneys, or genitals. Heart defects include problems with the heart valves, which control blood flow in the heart; the chambers of the heart that pump blood to the body (ventricles); or the dividing wall between the sides of the heart (the septum). Most children with Schinzel-Giedion syndrome have an accumulation of urine in the kidneys (hydronephrosis), which can occur in one or both kidneys. Affected individuals can have genital abnormalities such as underdevelopment (hypoplasia) of the genitals. Affected boys may have the opening of the urethra on the underside of the penis (hypospadias).

Bone abnormalities are common in people with Schinzel-Giedion syndrome. The bones at the base of the skull are often abnormally hard or thick (sclerotic), or the joint between the bones at the base of the skull (occipital synchondrosis) can be abnormally wide. In addition, affected individuals may have broad ribs, abnormal collarbones (clavicles), inward- and upward-turning feet (clubfeet), or shortened bones in the arms or legs or at the ends of the fingers (hypoplastic distal phalanges).

Children with Schinzel-Giedion syndrome who survive past infancy have a higher than normal risk of developing certain types of brain tumors called neuroepithelial tumors.

ORPHANET DEFINITION A rare multiple congenital anomalies/dysmorphic syndrome characterized by a distinctive facial dysmorphism, hydronephrosis, severe developmental delay, typical skeletal malformations, and genital and cardiac anomalies.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: <1 / 1 000 000; Worldwide; Class only. Prevalence at birth: 1-9 / 100 000; Europe; Class only. Reported case(s): 46.0; Worldwide. This is a published case count, not prevalence.

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.

Broad forehead · Very frequent (99-80%)

Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.

Broad nasal tip · Very frequent (99-80%)

Increase in width of the nasal tip.

Frontal bossing · Very frequent (99-80%)

Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.

Midface retrusion · Very frequent (99-80%)

Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.

Neurodevelopmental delay · Very frequent (99-80%)

Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems.

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

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

Short nose · Very frequent (99-80%)

Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.

Abnormal heart morphology · Frequent (79-30%)

Any structural anomaly of the heart.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormal helix morphology (Frequent (79-30%)); Abnormality of the genital system (Frequent (79-30%)); Abnormality of the outer ear (Frequent (79-30%)); Broad ribs (Frequent (79-30%)); Facial hemangioma (Frequent (79-30%)); Generalized hypertrichosis (Frequent (79-30%)); Hydronephrosis (Frequent (79-30%)); Hypertelorism (Frequent (79-30%)); Hypoplasia of the corpus callosum (Frequent (79-30%)); Low-set ears (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: <1 / 1 000 000; Worldwide; Class only. Prevalence at birth: 1-9 / 100 000; Europe; Class only. Reported case(s): 46.0; Worldwide. This is a published case count, not prevalence.

Which doctor should you see?

The suggested department for discussing Schinzel-Giedion syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with 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.

• 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 Schinzel-Giedion 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.