SSR4-CDG

What it is

From: Orphanet

SSR4-CDG is a form of congenital disorders of N-linked glycosylation characterized by neurologic abnormalities (global developmental delay in language, social skills and fine and gross motor development, intellectual disability, hypotonia, microcephaly, seizures/epilepsy), facial dysmorphism (deep set eyes, large ears, hypoplastic vermillion of upper lip, large mouth with widely spaced teeth), feeding problems often due to chewing difficulties and aversion to food with certain textures, failure to thrive, gastrointestinal abnormalities (reflux or vomiting) and strabismus. The disease is caused by mutations in the gene SSR4 (Xq28).

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 · Obligate (100%)

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

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

An abnormality of the gastrointestinal tract.

Abnormality of upper lip vermillion · Very frequent (99-80%)

An abnormality of the vermilion border, the sharp demarcation between the lip (red colored) and the adjacent normal skin.

Deeply set eye · Very frequent (99-80%)

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

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

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

Feeding difficulties · Very frequent (99-80%)

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Gastroesophageal reflux · Very frequent (99-80%)

A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.

Generalized hypotonia · Obligate (100%)

Generalized muscular hypotonia (abnormally low muscle tone).

Global developmental delay · Obligate (100%)

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.

Intellectual disability · Obligate (100%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Macrotia · Very frequent (99-80%)

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).

Microcephaly · Obligate (100%)

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

Strabismus · Very frequent (99-80%)

A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Vomiting · Very frequent (99-80%)

Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.

Other findings in the same source

From: Orphanet

Additional reported features include Wide mouth (Very frequent (99-80%)); Widely spaced teeth (Very frequent (99-80%)); Seizure (Frequent (79-30%)); Abnormal periventricular white matter morphology (Occasional (29-5%)); Abnormality of coagulation (Occasional (29-5%)); Abnormality of the cardiovascular system (Occasional (29-5%)); Abnormality of the skeletal system (Occasional (29-5%)); Absent septum pellucidum (Occasional (29-5%)); Horseshoe kidney (Occasional (29-5%)); Hypoplasia of the corpus callosum (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

X-linked recessive

Frequency and the population described

From: Orphanet

Reported case(s): 9.0; 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 X-linked recessive pattern involves a gene on the X chromosome. The number of X chromosomes and the particular genetic change influence how a condition is expressed. A genetic counsellor should interpret the result and the family history before discussing risks for relatives or future pregnancies.

Which doctor should you see?

The suggested department for discussing SSR4-CDG 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 SSR4-CDG. 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.