Wolf-Hirschhorn syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Wolf-Hirschhorn syndrome is a condition that affects many parts of the body. The major features of this disorder include a characteristic facial features, delayed growth and development, intellectual disability, and seizures.

Almost everyone with this disorder has distinctive facial features, including a broad nasal bridge, large and protruding eyes, and a high forehead. This combination is described as a "Greek warrior helmet" appearance. Other characteristic facial features include a shortened distance between the nose and upper lip (a short philtrum), a downturned mouth, a small chin (micrognathia), and poorly formed ears with small holes (pits) or flaps of skin (tags). Additionally, affected individuals may have asymmetrical facial features and an unusually small head (microcephaly).

People with Wolf-Hirschhorn syndrome experience delayed growth and development. Slow growth begins before birth, and affected infants tend to have problems feeding and gaining weight (failure to thrive). They also have weak muscle tone (hypotonia) and underdeveloped muscles. Motor skills such as sitting, standing, and walking are significantly delayed. Most children and adults with this disorder also have short stature.

Intellectual disability ranges from mild to severe in people with Wolf-Hirschhorn syndrome. Compared to people with other forms of intellectual disability, their socialization skills are strong, but verbal communication and language skills tend to be weaker. Most affected children also have seizures, which may be resistant to treatment. Seizures tend to disappear with age.

Additional features of Wolf-Hirschhorn syndrome include skin changes, such as mottled or dry skin; skeletal abnormalities, such as abnormal curvature of the spine (scoliosis and kyphosis); dental problems including, missing teeth; and an opening in the roof of the mouth (cleft palate) and/or a split in the upper lip (cleft lip). Wolf-Hirschhorn syndrome can also cause abnormalities of the eyes, heart, and genitourinary tract.

A condition called Pitt-Rogers-Danks syndrome has features that overlap with those of Wolf-Hirschhorn syndrome. Researchers now recognize that these two conditions are actually part of a single syndrome with variable signs and symptoms.

ORPHANET DEFINITION A developmental disorder characterized by typical craniofacial features, prenatal and postnatal growth impairment, intellectual disability, severe delayed psychomotor development, seizures, and hypotonia.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Not inherited

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Prevalence at birth: 1-9 / 100 000; Europe; Value and class. Point prevalence: 1-9 / 100 000; Europe; Class only.

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 lip morphology · Very frequent (99-80%)

An abnormality of the lip.

Abnormality of the mouth · Very frequent (99-80%)

An abnormality of the mouth.

Abnormality of the philtrum · Very frequent (99-80%)

An abnormality of the philtrum.

Ataxia · Very frequent (99-80%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Decreased fetal movement · Very frequent (99-80%)

An abnormal reduction in quantity or strength of fetal movements.

Dolichocephaly · Very frequent (99-80%)

An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.

Downslanted palpebral fissures · Very frequent (99-80%)

The palpebral fissure inclination is more than two standard deviations below the mean.

Downturned corners of mouth · Very frequent (99-80%)

A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.

Epicanthus · Very frequent (99-80%)

A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus.

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

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

Frontal bossing · Very frequent (99-80%)

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

Global developmental delay · Very frequent (99-80%)

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.

High anterior hairline · Very frequent (99-80%)

Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.

High forehead · Very frequent (99-80%)

An abnormally increased height of the forehead.

Other findings in the same source

From: Orphanet

Additional reported features include Highly arched eyebrow (Very frequent (99-80%)); Hypertelorism (Very frequent (99-80%)); Hypodontia (Very frequent (99-80%)); Hypospadias (Very frequent (99-80%)); Hypotonia (Very frequent (99-80%)); Intellectual disability, severe (Very frequent (99-80%)); Intrauterine growth retardation (Very frequent (99-80%)); Low posterior hairline (Very frequent (99-80%)); Microcephaly (Very frequent (99-80%)); Micrognathia (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; 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

Prevalence at birth: 1-9 / 100 000; Europe; Value and class. Point prevalence: 1-9 / 100 000; Europe; Class only.

Which doctor should you see?

The suggested department for discussing Wolf-Hirschhorn 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

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

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.