Terminal osseous dysplasia-pigmentary defects syndrome

What it is

From: Orphanet

A rare acromelic dysplasia characterized by abnormal and/or delayed ossification of bones primarily in the hands and feet (that may lead to brachydactyly, camptodactyly, and clinodactyly), severe limb deformities, joint contractures, pigmentary skin lesions on the face and scalp and digital fibromatosis of the fingers and toes which appear a few months after birth. While the skeletal manifestations primarily affect the hands and feet, more generalized bone involvement including mesomelic bowing and/or shortening of the arms and legs have also been reported. Some patients may also present with craniofacial dysmorphism including midface hypoplasia, hypertelorism, ptosis, coloboma of the iris and eyelids, low-set ears, depressed nasal bridge, and multiple hypertrophic frenula. Additional clinical features may include short stature, short broad thorax, scoliosis, atrial septal defect and ventricular septal hypertrophy, pulmonary artery stenosis and anal stenosis.

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.

Hyperpigmented papule · Very frequent (99-80%)

A papule (circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point) that exhibits increased pigmentation (is darker) compared to the surrounding skin.

Inclusion body fibromatosis · Very frequent (99-80%)

A benign tumor made up of mostly myofibroblasts that appears almost exclusively on the digits of the hands and feet, rarely involving the thumb or big toe. The lesion displays a proliferation of bland intradermal spindle cells arranged in whorls, fascicles, or a storiform pattern in a collagenous background of varying degrees. Also usually present are perpendicular tumor cell fascicles that extend to the epidermis. The small intracytoplasmic inclusions are said to appear similar to red blood cells. The inclusion bodies have been shown to be made up of densely packed vimentin and actin filaments. The tumor often causes a dome-shaped elevation of the overlying structures, forming a protuberant or polypoid nodule. The overlying epidermis can display a host of changes, including acanthosis, hyperkeratosis, parakeratosis, rete ridge flattening, entrapment of adnexal structures, and, rarely, ulceration.

Accessory oral frenulum · Frequent (79-30%)

Extra fold of tissue extending from the alveolar ridge to the inner surface of the upper or lower lip.

Alopecia · Frequent (79-30%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Brachydactyly · Frequent (79-30%)

Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

Clinodactyly · Frequent (79-30%)

An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).

Flexion contracture · Frequent (79-30%)

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

Camptodactyly · Occasional (29-5%)

The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.

Depressed nasal tip · Occasional (29-5%)

Decreased distance from the nasal tip to the nasal base.

Epicanthus · Occasional (29-5%)

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.

Hypertelorism · Occasional (29-5%)

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Hypoplasia of teeth · Occasional (29-5%)

Developmental hypoplasia of teeth.

Iris coloboma · Occasional (29-5%)

A coloboma of the iris.

Patent foramen ovale · Occasional (29-5%)

Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.

Other findings in the same source

From: Orphanet

Additional reported features include Preauricular pit (Occasional (29-5%)); Scoliosis (Occasional (29-5%)); Short stature (Occasional (29-5%)); Short thorax (Occasional (29-5%)); Syndactyly (Occasional (29-5%)); Osteolysis involving bones of the lower limbs (Occasional (29-5%)); Osteolysis involving bones of the upper limbs (Occasional (29-5%)); Mitral regurgitation (Very rare (<4-1%)); Restrictive cardiomyopathy (Very rare (<4-1%)). 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 dominant

Frequency and the population described

From: Orphanet

Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An X-linked dominant pattern involves a gene on the X chromosome. Expression can differ between individuals and between sexes. Family counselling requires the actual genetic finding and a clear family history; a general description cannot calculate the risk or severity for a particular child.

Which doctor should you see?

The suggested department for discussing Terminal osseous dysplasia-pigmentary defects syndrome is Orthopaedics, with a orthopaedic specialist 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.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Terminal osseous dysplasia-pigmentary defects 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.