Chondrodysplasia-difference of sex development syndrome

What it is

From: Orphanet

A rare difference of sex development affecting 46,XY individuals and characterized by complete gonadal dysgenesis (normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) in association with severe dwarfism with generalized chondrodysplasia (bell-shaped thorax, micromelia, brachydactyly). Other reported features in the live sibling included eye anomalies (hypoplastic irides, myopia, coloboma of optic discs), dysmorphic features (deep-set eyes, upslanting palpebral fissures, puffy eyelids, large ears and mouth, mild prognathism), muscular hypoplasia, mild intellectual deficiency and severe microcephaly with cerebellar vermis hypoplasia.

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.

Abnormality of pelvic girdle bone morphology · Very frequent (99-80%)

An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.

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

An abnormality of the shoulder, which is defined as the structures surrounding the shoulder joint where the humerus attaches to the scapula.

Broad long bones · Very frequent (99-80%)

Increased cross-section (diameter) of the long bones. Note that widening may primarily affect specific regions of long bones (e.g., diaphysis or metaphysis), but this should be coded separately.

Increased skull ossification · Very frequent (99-80%)

An increase in the magnitude or amount of ossification of the skull.

Intellectual disability · Very frequent (99-80%)

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.

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

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

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 · Very frequent (99-80%)

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

Micromelia · Very frequent (99-80%)

The presence of abnormally small extremities.

Narrow chest · Very frequent (99-80%)

Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.

Severe short stature · Very frequent (99-80%)

A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.

Short metacarpal · Very frequent (99-80%)

Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.

Short phalanx of finger · Very frequent (99-80%)

Short (hypoplastic) phalanx of finger, affecting one or more phalanges.

Telecanthus · Very frequent (99-80%)

Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.

Other findings in the same source

From: Orphanet

Additional reported features include Blepharophimosis (Frequent (79-30%)); Cerebral hypoplasia (Frequent (79-30%)); Chorioretinal coloboma (Frequent (79-30%)); Deeply set eye (Frequent (79-30%)); Hypoplasia of the iris (Frequent (79-30%)); Male pseudohermaphroditism (Frequent (79-30%)); Miosis (Frequent (79-30%)); Strabismus (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Antenatal; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

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.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Chondrodysplasia-difference of sex development 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 Chondrodysplasia-difference of sex development 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.