Combined immunodeficiency with facio-oculo-skeletal anomalies

What it is

From: Orphanet

A rare combined immunodeficiency disorder characterized by primary immunodeficiency manifesting with repeated bacterial, viral and fungal infections, in association with neurological manifestations (hypotonia, cerebellar ataxia, myoclonic seizures), developmental delay, optic atrophy, facial dysmorphism (high forehead, hypoplastic supraorbital ridges, palpebral edema, hypertelorism, flat nasal bridge, broad nasal root and tip, anteverted nares, thin lower lip overlapped by upper lip, square chin) and skeletal anomalies (short metacarpals/metatarsals with cone-shaped epiphyses, osteopenia).

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 T cell subset distribution · Frequent (79-30%)

Abnormal increase or decrease of absolute number (either count per volume or percentage of total lymphocytes) of any T cell subpopulation, commonly characterized as CD3+ lymphocytes, in the blood, compared to a reference range for a given sex and age-group.

Abnormal facial shape · Frequent (79-30%)

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

Abnormality of the chin · Frequent (79-30%)

An abnormality of the chin, i.e., of the inferior portion of the face lying inferior to the lower lip and including the central prominence of the lower jaw.

Abnormality of the skeletal system · Frequent (79-30%)

An abnormality of the skeletal system.

Anteverted nares · Frequent (79-30%)

Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).

Arthritis · Frequent (79-30%)

Inflammation of a joint.

Ataxia · Frequent (79-30%)

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).

Broad middle phalanx of finger · Frequent (79-30%)

Increased width of the middle phalanx of finger.

Broad nasal tip · Frequent (79-30%)

Increase in width of the nasal tip.

Chronic oral candidiasis · Frequent (79-30%)

Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.

Combined immunodeficiency · Frequent (79-30%)

A group of phenotypically heterogeneous genetic disorders characterized by profound deficiencies of T- and B-cell function, which predispose the patients to both infectious and noninfectious complications.

Cone-shaped epiphysis · Frequent (79-30%)

Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.

Decreased circulating antibody level · Frequent (79-30%)

An abnormally decreased level of immunoglobulin in blood.

Decreased circulating total IgA · Frequent (79-30%)

Undetectable serum immunoglobulin A level at a value < 5 mg/dL (0.05 g/L).

Other findings in the same source

From: Orphanet

Additional reported features include Decreased circulating total IgG (Frequent (79-30%)); Decreased circulating total IgM (Frequent (79-30%)); Decreased lymphocyte proliferation in response to anti-CD3 (Frequent (79-30%)); Decreased lymphocyte proliferation in response to mitogen (Frequent (79-30%)); Decreased proportion of CD4-positive T cells (Frequent (79-30%)); Decreased specific antibody response to vaccination (Frequent (79-30%)); Decreased total B cell count (Frequent (79-30%)); Deeply set eye (Frequent (79-30%)); Depressed nasal bridge (Frequent (79-30%)); Dermatochalasis (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Neonatal

Inheritance in the source

From: Orphanet

Multigenic/multifactorial

Frequency and the population described

From: Orphanet

Reported case(s): 2.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing Combined immunodeficiency with facio-oculo-skeletal anomalies 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 Combined immunodeficiency with facio-oculo-skeletal anomalies. 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.