RAPADILINO syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

RAPADILINO syndrome is a rare condition that involves many parts of the body. Bone development is especially affected, causing many of the characteristic features of the condition.

Most affected individuals have underdevelopment or absence of the bones in the forearms and the thumbs, which are known as radial ray malformations. The kneecaps (patellae) can also be underdeveloped or absent. Other features include an opening in the roof of the mouth (cleft palate) or a high arched palate; a long, slender nose; and dislocated joints.

Many infants with RAPADILINO syndrome have difficulty feeding and experience diarrhea and vomiting. The combination of impaired bone development and feeding problems leads to slow growth and short stature in affected individuals.

Some individuals with RAPADILINO syndrome have harmless light brown patches of skin that resemble a skin finding known as café-au-lait spots. In addition, people with RAPADILINO syndrome have a slightly increased risk of developing a type of bone cancer known as osteosarcoma or a blood-related cancer called lymphoma. In individuals with RAPADILINO syndrome, osteosarcoma most often develops during childhood or adolescence, and lymphoma typically develops in young adulthood.

The condition name is an acronym for the characteristic features of the disorder: RA for radial ray malformations, PA for patella and palate abnormalities, DI for diarrhea and dislocated joints, LI for limb abnormalities and little size, and NO for slender nose and normal intelligence.

The varied signs and symptoms of RAPADILINO syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and Rothmund-Thomson syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the RECQL4 gene cause RAPADILINO syndrome. This gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division and for repairing damaged DNA. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.

The most common RECQL4 gene mutation involved in RAPADILINO syndrome causes the RECQL4 protein to be pieced together incorrectly. This genetic change results in the production of a protein that is missing a region called exon 7 and is unable to act as a helicase. The loss of helicase function may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. These changes may result in the accumulation of DNA errors and cell death, although it is unclear exactly how RECQL4 gene mutations lead to the specific features of RAPADILINO syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

RAPADILINO syndrome is a rare condition, although its worldwide prevalence is unknown. The condition was first identified in Finland, where it affects an estimated 1 in 75,000 individuals, although it has since been found in other regions.

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.

Intrauterine growth retardation · Very frequent (99-80%)

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Postnatal growth retardation · Very frequent (99-80%)

Slow or limited growth after birth.

Aplasia/Hypoplasia of the patella · Frequent (79-30%)

Absence or underdevelopment of the patella.

Aplasia/Hypoplasia of the radius · Frequent (79-30%)

A small/hypoplastic or absent/aplastic radius.

Aplasia/Hypoplasia of the thumb · Frequent (79-30%)

Hypoplastic/small or absent thumb.

Cleft palate · Frequent (79-30%)

Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Diarrhea · Frequent (79-30%)

Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.

Feeding difficulties · Frequent (79-30%)

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

Other findings in the same source

From: Orphanet

Additional reported features include High palate (Frequent (79-30%)); Abnormality of limbs (Frequent (79-30%)); Slender nose (Frequent (79-30%)); Decreased circulating antibody level (Occasional (29-5%)); Decreased total T cell count (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing RAPADILINO 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 RAPADILINO 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.