High-yield overview

The 'Stippled Epiphyses' Dysplasias

Stippled epiphysesPunctate calcification in infancy - resolves with growth

RCDP1 to RCDP5PEX7, GNPAT, AGPS, FAR1, PEX5L

Plasmalogen grades itNegligible = classic severe; higher = nonclassic, milder

Conradi = asymmetricX-linked dominant EBP; limb discrepancy

Forms (with shared hallmark)

Hallmark

PatternStippled (punctate) epiphyseal and peri-articular calcification on infant radiographs, which typically resolves with age: the unifying radiographic feature of an otherwise heterogeneous group.

Treatment

Rhizomelic CDP

PatternSevere autosomal-recessive peroxisomal defect of plasmalogen synthesis: symmetric rhizomelic (proximal) limb shortening, profound developmental delay, cataracts and contractures, often with early death.

Treatment

Conradi-Hunermann (CDPX2)

PatternX-linked dominant (EBP gene), mostly females: asymmetric limb shortening with limb-length discrepancy, scoliosis, ichthyosis and cataracts. Milder and survivable.

Treatment

X-linked recessive & teratogenic

PatternX-linked recessive brachytelephalangic form (ARSL/ARSE) with nasal and distal-phalangeal hypoplasia. Warfarin embryopathy and maternal autoimmune disease (e.g. SLE) phenocopy CDP.

Treatment

Critical Must-Knows

Chondrodysplasia punctata (CDP) is a heterogeneous group of skeletal dysplasias unified by one radiographic hallmark in infancy: stippled (punctate) epiphyseal and peri-articular calcification, which characteristically resolves as the child grows.
The rhizomelic form is the most severe, and it is a spectrum: an autosomal-recessive peroxisomal disorder of plasmalogen synthesis in five types (PEX7, GNPAT, AGPS, FAR1, PEX5L). Classic disease, with negligible plasmalogens, is severe and often fatal early; nonclassic patients with higher residual plasmalogens have better growth and cognition and survive longer, so counselling waits for the level.
Conradi-Hunermann syndrome (CDPX2) is X-linked dominant (EBP), affects mostly females (often lethal in males) and is survivable. Asymmetry is the clue: asymmetric limb shortening and discrepancy, scoliosis, ichthyosis along Blaschko's lines and cataracts.
An X-linked recessive (brachytelephalangic) form and the teratogenic phenocopies, warfarin embryopathy and maternal autoimmune disease such as SLE, complete the group, so a maternal drug and autoimmune history matters.
The orthopaedic sequelae depend on the form: rhizomelic or asymmetric limb shortening and discrepancy, scoliosis (especially Conradi-Hunermann), joint contractures and, in milder survivors, deformity.
Management is largely supportive, form-dependent and multidisciplinary: genetic and metabolic diagnosis, epiphysiodesis or lengthening, scoliosis and contracture care in survivable forms, cataract surgery and family counselling, with the severe rhizomelic form largely palliative.

Clinical Pearls

“
Stippled (punctate) epiphyses in infancy = chondrodysplasia punctata, a heterogeneous group; the stippling resolves with age.
“
Rhizomelic CDP = AR peroxisomal plasmalogen defect (RCDP1-5), graded by residual plasmalogen. Conradi-Hunermann (CDPX2) = X-linked dominant EBP, females, asymmetric shortening, ichthyosis, cataracts.
“
Ask about the mother: warfarin embryopathy and maternal SLE/autoimmune disease phenocopy CDP. Orthopaedic work = discrepancy, scoliosis, contractures.

Overview & Epidemiology

Chondrodysplasia punctata is a group of disorders that share one radiographic sign: stippled epiphyseal calcification in infancy. The sign is produced by defects in peroxisomal plasmalogen synthesis, cholesterol biosynthesis or arylsulfatase function, or by teratogenic insult.

How rare. All forms are rare orphan diseases, and no reliable population incidence could be found for any of them. CDP sits among the less common skeletal dysplasias met in fetal and neonatal practice: in the Jezova 10-year perinatal series, thanatophoric dysplasia and osteogenesis imperfecta made up about half of the autopsy cases, and CDP was among the less frequent diagnoses.

Where it sits. More than 400 genetic skeletal disorders are recognised in the current classification, and an increasing proportion are confirmed by genetic testing.

Who gets which form. The rhizomelic forms are autosomal recessive and affect either sex, and the brachytelephalangic form (CDPX1) is X-linked recessive. Conradi-Hünermann (CDPX2) is X-linked dominant and seen almost entirely in females, because hemizygous males rarely survive. The teratogenic phenocopies follow maternal exposures, warfarin or autoimmune disease, rather than any inheritance.

Pathophysiology: The Metabolic Basis of Each Form

Rhizomelic CDP is a plasmalogen defect. It is a peroxisomal disorder of plasmalogen (ether-phospholipid) biosynthesis, and it is subdivided by the step that fails. The result is deficient plasmalogens, with raised phytanic acid in type 1.

RCDP1 - PEX7, the PTS2 receptor that imports the plasmalogen-synthesis enzymes into the peroxisome
RCDP2 - GNPAT, RCDP3 - AGPS and RCDP4 - FAR1, the enzymes themselves
RCDP5 - PEX5L, loss of the long isoform of PEX5, which co-receptors PTS2 import and so mimics PEX7 loss

Why RCDP5 is not Zellweger. Other PEX5 mutations cause Zellweger spectrum disease. Losing only PEX5L knocks out import of PTS2-tagged proteins alone, the same functional lesion as PEX7 loss, so it produces RCDP instead. RCDP5 was reported in four patients from two families.

Biochemical pathway diagram of plasmalogen biosynthesis across peroxisomal and endoplasmic-reticulum steps — Plasmalogen synthesis. The first steps, from DHAP through 1-acyl-DHAP to 1-alkyl-DHAP (acyl-DHAP synthase, then alkyl-DHAP synthase), take place in the peroxisome; the remainder, ending in the ethanolamine (PlsEtn) and choline (PlsCho) plasmalogens shown in red, takes place in the endoplasmic reticulum. RCDP interrupts the early ether-lipid steps.Credit: Chen et al., Nutrients 2025 (CC BY 4.0)

Peroxisome pathway diagram showing GNPAT and AGPS in ether-phospholipid synthesis — The peroxisomal map places GNPAT and AGPS directly in ether-phospholipid synthesis, from DHAP to alkyl-DHAP, and separates that pathway from very-long-chain fatty-acid β-oxidation and catalase-driven reactive-oxygen metabolism. The ether lipid is completed in the endoplasmic reticulum.Credit: Sarkar and Lipinski, Cells 2024 (CC BY 4.0)

Conradi-Hünermann is a cholesterol-synthesis defect. EBP encodes emopamil-binding protein, a sterol Δ8-Δ7 isomerase in the post-squalene cholesterol biosynthesis pathway, and its deficiency causes accumulation of sterol precursors that can be measured in plasma. The male lethality reflects the essential cholesterol pathway, and the Blaschko-line skin reflects X-inactivation mosaicism in surviving females.

Why the epiphyses are stippled. The punctate calcification is abnormal, ectopic calcific deposition within the unossified epiphyseal cartilage. It resolves as the cartilage ossifies normally with growth.

Clinical Presentation: The Forms & Their Features

The hallmark. Every form shares stippled (punctate) epiphyseal and peri-articular calcification on the infant radiograph. The pattern of limb shortening suggests the form: symmetric and rhizomelic in RCDP, asymmetric in Conradi-Hünermann. The hallmark may be most conspicuous in the distal skeleton, with dense puncta around the unossified tarsal and phalangeal centres.

Neonatal chest (A) and abdominal (B) radiographs showing stippled calcification along the upper spine, with arrows at both shoulder regions — Neonatal chest (A) and abdominal (B) radiographs. Stippled calcification runs along the upper spine, and the arrows point to both shoulder regions.Credit: Olarte Bermúdez et al., Cureus 2025 (CC BY 4.0)

Magnified radiographs of the spine (A), shoulder and humerus (B) and pelvis (C) showing punctate calcification, arrowed in B and C — Magnified views from the same report: (A) punctate calcification along the thoracolumbar vertebrae; (B) the shoulder girdle and humerus, with the stippling arrowed; (C) the pelvis, with arrows on the stippling at both hips.Credit: Olarte Bermúdez et al., Cureus 2025 (CC BY 4.0)

Lateral radiograph of an infant's foot and ankle showing clusters of punctate calcification in the tarsal region — Lateral radiograph of an infant's foot and ankle: clusters of punctate calcification in the hindfoot and midfoot, the largest in the heel.Credit: Handa et al., Japanese Journal of Radiology 2022 (CC BY 4.0)

Rhizomelic CDP (RCDP1-5)

Genetics: Autosomal recessive peroxisomal: PEX7, GNPAT, AGPS, FAR1, PEX5L
Key features: A spectrum graded by residual plasmalogen - classic: symmetric rhizomelia, delay, cataracts, early death; nonclassic: milder, better growth and cognition

Conradi-Hunermann (CDPX2)

Genetics: X-linked dominant (EBP); mostly females
Key features: Asymmetric limb shortening (discrepancy), scoliosis, ichthyosis, cataracts; milder

X-linked recessive (CDPX1)

Genetics: ARSL/arylsulfatase
Key features: Brachytelephalangic - nasal + distal-phalangeal hypoplasia

Teratogenic/secondary

Genetics: Warfarin embryopathy; maternal autoimmune (SLE)
Key features: Phenocopy of CDP - take maternal history

Main Forms of Chondrodysplasia Punctata
Form	Genetics	Key features
Rhizomelic CDP (RCDP1-5)	Autosomal recessive peroxisomal: PEX7, GNPAT, AGPS, FAR1, PEX5L	A spectrum graded by residual plasmalogen - classic: symmetric rhizomelia, delay, cataracts, early death; nonclassic: milder, better growth and cognition
Conradi-Hunermann (CDPX2)	X-linked dominant (EBP); mostly females	Asymmetric limb shortening (discrepancy), scoliosis, ichthyosis, cataracts; milder
X-linked recessive (CDPX1)	ARSL/arylsulfatase	Brachytelephalangic - nasal + distal-phalangeal hypoplasia
Teratogenic/secondary	Warfarin embryopathy; maternal autoimmune (SLE)	Phenocopy of CDP - take maternal history

Reading the pattern. Conradi-Hünermann is recognised by its asymmetry, and its ichthyosis follows Blaschko's lines. Its asymmetric shortening, limb-length discrepancy and scoliosis generate real orthopaedic work in deformity and discrepancy correction.

The Stippling Tells You the Group - the Pattern and the History Tell You the Form

The stippling identifies chondrodysplasia punctata as a group but does not by itself determine prognosis or management, because the forms differ enormously. Maternal warfarin in pregnancy and maternal autoimmune disease such as systemic lupus erythematosus can produce stippled epiphyses, so a maternal drug and autoimmune history must be taken.

Rhizomelic CDP: A Spectrum Graded by Plasmalogen

Classic disease. Severe (classic) RCDP has negligible plasmalogen levels, with congenital cataracts, skeletal dysplasia, growth failure and neurodevelopmental deficit. In its classic form it is often lethal in early childhood.

Nonclassic disease. Individuals with milder or nonclassic RCDP have higher residual plasmalogen levels, better growth and better cognitive outcomes, and survive well beyond infancy. Plasmalogen deficiency is itself described as the main pathogenic factor determining severity, so the red-cell plasmalogen level is a prognostic test as well as a diagnostic one. No reliable survival figure for the group could be found.

Nonclassic rhizomelic CDP exists, and the biochemistry predicts which child you have

Calling the rhizomelic form uniformly severe and early-lethal is the traditional teaching, and it is wrong at the milder end. Do not answer "rhizomelic CDP is lethal in infancy" flatly: call it a spectrum graded by residual plasmalogen, and do not counsel a family from the classic phenotype before the biochemistry is known.

The brain. In the severe phenotype, MRI shows supratentorial white-matter abnormality with a parieto-occipital predominance, and cerebellar atrophy appears in older patients. This is a progressive peroxisomal leukoencephalopathy rather than a purely skeletal condition, which matters when a child with stippled epiphyses also has neurological signs.

The skeleton. The reported cases below show the rhizomelic pattern. The RCDP3 survey combines bilateral proximal-limb shortening with punctate ossification around the hips, knees and shoulders, and RCDP2 may present with extensive vertebral and periarticular stippling across the chest and abdomen. Short humeri, flared metaphyses and punctate proximal and distal epiphyses define the rhizomelic upper limb, while the lower limbs show bilateral femoral shortening, metaphyseal flaring and stippling at both ends of the bone. In the neonatal case shown under Clinical Presentation, vertebral, humeral and pelvic stippling came with rhizomelic shortening and shallow acetabular development.

RCDP3 skeletal survey in eight panels (A-H) covering the upper limbs, pelvis and lower limbs, chest, spine and skull, with short femora in panel C — Skeletal survey in RCDP3, panels A to H with scale bars: upper limbs (A, B), pelvis and lower limbs (C), chest and spine (D to F) and skull (G, H). The femora in C are short.Credit: Shawli et al., Cureus 2021 (CC BY 3.0)

Neonatal chest and abdominal radiograph showing extensive vertebral punctate calcification in RCDP2 — RCDP2: frontal chest and abdominal radiograph with dense punctate calcification along the thoracic and lumbar spine.Credit: Sayed et al., Clinical Case Reports 2023 (CC BY 4.0)

Frontal radiograph of an infant's chest and upper limbs showing short humeri with flared metaphyses and stippled proximal humeral ends in RCDP2 — RCDP2, upper limbs: both humeri are short with flared metaphyses, and their proximal ends are stippled. The spine is stippled too.Credit: Sayed et al., Clinical Case Reports 2023 (CC BY 4.0)

Frontal radiograph of an infant's pelvis and lower limbs showing short femora with broad metaphyses — Frontal radiograph of the pelvis and lower limbs: the femora are short, with broad metaphyses.Credit: Javaid et al., Cureus 2022 (CC BY 4.0)

Frontal radiograph of an infant's trunk and upper limbs showing short humeri with broad metaphyses and punctate calcification at the proximal humeral ends — From the same report, the trunk and upper limbs: short humeri with broad metaphyses and punctate calcification at the proximal humeral ends.Credit: Javaid et al., Cureus 2022 (CC BY 4.0)

Investigations

Radiographs are the entry point. Stippling in an infant identifies the group, and the pattern of limb shortening suggests the form. Later films show the sequelae (shortening, discrepancy, scoliosis) rather than the sign.

Confirming the form. Biochemistry, genetics and the maternal history do the rest:

Peroxisomal biochemistry for suspected rhizomelic disease: low red-cell plasmalogens, with raised phytanic acid in type 1, confirmed in cultured fibroblasts. The residual plasmalogen level also grades severity. Any peroxisomal disorder is diagnosed on a battery of blood and urine assays confirmed in cultured fibroblasts and by DNA analysis.
Plasma sterol profile for suspected Conradi-Hünermann: accumulation of 8-dehydrocholesterol and 8(9)-cholestenol points to EBP.
Genetic testing confirms the form: GNPAT, AGPS or FAR1 for RCDP2-4, EBP for CDPX2 and ARSL for CDPX1. RCDP1 and RCDP5 overlap biochemically, so a selective PTS2-import defect warrants sequencing both PEX7 and PEX5 exon 9.
Maternal history is an investigation in its own right: first-trimester warfarin, maternal autoimmune disease (SLE), vitamin-K deficiency and certain anticonvulsants.
Hip ultrasound can demonstrate punctate femoral-head calcification before the ossific nuclei are fully visible on radiographs.
Cervical MRI evaluates craniovertebral narrowing and confirms whether dysplastic bone is moulding or compressing the cord.
Brain MRI when neurological signs are present, looking for the white-matter and cerebellar changes of severe RCDP.

Bilateral hip ultrasound showing punctate calcification within both femoral head epiphyses — Hip ultrasound, right (RT) and left (LT): the bright echogenic foci within both cartilaginous femoral heads are the punctate calcification.Credit: Sayed et al., Clinical Case Reports 2023 (CC BY 4.0)

Sagittal cervical MRI showing reduced foramen magnum calibre in Conradi-Hünermann-Happle syndrome — Sagittal MRI of the craniocervical junction and cervical spine in Conradi-Hünermann-Happle syndrome. The arrow marks the reduced calibre at the foramen magnum.Credit: Hatia et al., Cureus 2024 (CC BY 4.0)

Frontal radiograph of the skull, cervical and thoracic spine in CDPX2, with stars, squares and an arrow marking costal and vertebral abnormalities — In CDPX2, the infant radiograph may combine persistent costal and vertebral stippling with scoliosis and segmentation abnormalities. On this frontal radiograph of the skull, cervical and thoracic spine, stars, squares and an arrow mark the abnormal areas.Credit: Hatia et al., Cureus 2024 (CC BY 4.0)

Warfarin Embryopathy and the Fuller Differential

How warfarin does it. Warfarin crosses the placenta and inhibits vitamin-K epoxide reductase, impairing γ-carboxylation of the vitamin-K-dependent bone protein matrix Gla protein, a normal inhibitor of cartilage calcification. Cartilage then calcifies abnormally, giving stippled epiphyses and nasal hypoplasia (fetal warfarin syndrome).

The window. The critical teratogenic window is the first trimester (about 6-9 weeks), which is why heparin or LMWH, which do not cross the placenta, are substituted in pregnancy.

Other secondary causes. Maternal autoimmune disease (SLE), maternal vitamin-K deficiency and some anticonvulsants (phenytoin) can also produce a stippled-epiphyses phenocopy.

The fuller differential. Beyond CDP, stippled epiphyses raise:

Zellweger spectrum, another peroxisomal disorder
Congenital hypothyroidism (epiphyseal dysgenesis)
Trisomy 18 or 21
GM1 gangliosidosis
Congenital infection
The cholesterol-pathway disorders CHILD syndrome (NSDHL) and Smith-Lemli-Opitz (DHCR7)

Management

Classify, then support and correct. Management is largely supportive and form-dependent within a multidisciplinary team. Accurate classification, by genetic and metabolic testing plus the maternal history, guides both the prognosis and the plan.

The orthopaedic work. It falls in the survivable forms, especially Conradi-Hünermann:

Limb-length discrepancy, by epiphysiodesis or lengthening
Scoliosis
Contractures

The team. Alongside orthopaedics sit ophthalmology for the cataracts, dermatology for the ichthyosis, metabolic medicine and genetics, and family counselling.

The severe rhizomelic form. Care is largely supportive or palliative given the poor prognosis, and treatment of peroxisomal disorders remains largely symptomatic.

The cervical spine. The case below, of the brachytelephalangic form, had atlantoaxial instability with os odontoideum, an instability pattern that requires dedicated cervical assessment before correction. Radiographs, CT and MRI defined the dysplastic vertebrae, reducibility, bony anatomy and neural compression before occipitocervical fusion, and follow-up imaging confirmed stabilisation of the occiput-to-C2 segment, fusion and decompression.

Flexion and extension cervical radiographs showing atlantoaxial instability and os odontoideum in brachytelephalangic chondrodysplasia punctata — Dynamic lateral cervical radiographs (A, B), one in flexion and one in extension, with arrows at the atlantoaxial level.Credit: Fujimoto et al., Case Reports in Orthopedics 2019 (CC BY 4.0)

Preoperative cervical radiographs, hand radiograph, sagittal CT and sagittal and axial MRI in brachytelephalangic chondrodysplasia punctata — Preoperative work-up: frontal (A) and lateral (B to D) cervical radiographs, with arrowheads in A and B; a hand radiograph (E); sagittal CT with an arrow at the craniovertebral junction (F); and sagittal (G) and axial (H) MRI.Credit: Fujimoto et al., Case Reports in Orthopedics 2019 (CC BY 4.0)

Postoperative radiographs, CT and MRI after occipitocervical fusion for atlantoaxial instability — After occipitocervical fusion: lateral radiographs in two neck positions (A, B) show the occipital plate and rods anchored to upper cervical screws, followed by sagittal CT (C, arrow) and sagittal MRI (D).Credit: Fujimoto et al., Case Reports in Orthopedics 2019 (CC BY 4.0)

Complications

Orthopaedic. Limb-length discrepancy in the asymmetric forms, progressive scoliosis, joint contractures and hip instability.
Neurological. Profound developmental delay in classic RCDP, with the progressive leukoencephalopathy described above.
Ophthalmic. Congenital cataracts in both RCDP and CDPX2 threaten visual development and warrant early surgery.
Cutaneous. Ichthyosis along Blaschko's lines in CDPX2, usually improving with age.
Systemic. Feeding difficulties and recurrent respiratory infections in classic RCDP.

Right hip ultrasound in flexion showing a dislocated femoral head (arrow) in RCDP3 with bilateral femoral-head dislocation — Right hip ultrasound in flexion (labelled 'Right HIP Flex') from a case of RCDP3 with bilateral femoral-head dislocation. The arrow marks the dislocated right femoral head, the hip instability that can accompany severe rhizomelic disease.Credit: Shawli et al., Cureus 2021 (CC BY 3.0)

Mnemonics & Memory Aids

Mnemonic

STIPPLE

Stippled (punctate) epiphyses - the hallmark (resolves with age)

Teratogenic phenocopies - warfarin embryopathy, maternal autoimmune (SLE)

Ichthyosis + cataracts (Conradi-Hunermann)

Peroxisomal rhizomelic form (AR, RCDP1-5) - a spectrum: classic severe, nonclassic milder

Pattern: rhizomelic = symmetric; Conradi-Hunermann = asymmetric

Limb shortening/discrepancy + scoliosis + contractures (orthopaedic sequelae)

EBP gene (X-linked dominant Conradi-Hunermann); classify → manage by form

Hook:STIPPLE: Stippled epiphyses, Teratogenic phenocopies, Ichthyosis/cataracts, Peroxisomal rhizomelic (severe), Pattern (symmetric vs asymmetric), Limb sequelae, EBP gene.

Mnemonic

PGAFP

PEX7 - RCDP1 (the PTS2 receptor; the commonest type)

GNPAT - RCDP2

AGPS - RCDP3

FAR1 - RCDP4

PEX5L (long isoform) - RCDP5

Hook:PGAFP: the five rhizomelic types in order - PEX7, GNPAT, AGPS, FAR1, PEX5L. One receptor (PEX7), three enzymes, one co-receptor (PEX5L) - all fail plasmalogen synthesis.

Mnemonic

GLA

Gamma-carboxylation blocked - warfarin inhibits vitamin-K epoxide reductase

Loss of calcification inhibition - matrix Gla protein left undercarboxylated

Abnormal cartilage calcification - stippled epiphyses + nasal hypoplasia (fetal warfarin syndrome)

Hook:GLA: warfarin blocks Gamma-carboxylation, Loses the calcification inhibitor (matrix Gla protein), and cartilage calcifies Abnormally - first-trimester window, so substitute heparin/LMWH in pregnancy.

Clinical Decision Scenarios

Practise clinical reasoning and management decisions out loud

Viva scenarioStandard

Stippled Epiphyses in an Infant

Clinical prompt

“An infant radiograph shows stippled epiphyses. What is the diagnosis group, what forms do you consider, and what history is important?”

Exam day cheat sheet

Chondrodysplasia Punctata - Exam Day Cheat Sheet

Hallmark

Stippled (punctate) epiphyseal/peri-articular calcification in infancy
Heterogeneous group; stippling resolves with growth
Identify the form (prognosis/management differ greatly)

Genetic forms

Rhizomelic CDP: AR peroxisomal plasmalogen defect, RCDP1-5 (PEX7, GNPAT, AGPS, FAR1, PEX5L)
A SPECTRUM: classic (negligible plasmalogens) severe with early death; nonclassic (higher) milder - the level is prognostic
Conradi-Hunermann (CDPX2): X-linked dominant (EBP), females, asymmetric shortening + ichthyosis + cataracts
X-linked recessive (CDPX1, ARSL): brachytelephalangic (nasal/distal-phalangeal hypoplasia)

Secondary/teratogenic

Warfarin embryopathy (maternal warfarin in pregnancy)
Maternal autoimmune disease (e.g. SLE)
Take a maternal drug/autoimmune history

Orthopaedic management

Limb shortening/discrepancy (epiphysiodesis/lengthening)
Scoliosis and contractures (survivable forms)
Multidisciplinary: ophthalmology (cataracts), dermatology, genetics; severe form palliative

Evidence & Key Studies

Evidence

Skeletal dysplasias of the fetus and infant (including chondrodysplasia punctata)

Jezova M, Pavlovska D, Grochova I, Michenkova A, Vlasin P • Ceskoslovenska Patologie (2023)

Key Findings:

More than 400 genetic skeletal disorders are included in the latest classification; the most severe/lethal phenotypes are identifiable in the prenatal period, and perinatal autopsy/post-mortem radiographs are crucial for definitive diagnosis.
Chondrodysplasia punctata is among the recognised skeletal dysplasias encountered in fetal/neonatal practice (alongside thanatophoric dysplasia, osteogenesis imperfecta, campomelic dysplasia and achondroplasia).
An increasing number of cases are confirmed by genetic testing, reflecting the heterogeneous genetic basis of these dysplasias.

Clinical implication: CDP is a recognised fetal/neonatal skeletal dysplasia in which post-mortem radiographs and genetic testing secure the diagnosis - relevant to counselling and recurrence risk.

Verify on PubMed (PMID 37468326)

Main Forms of Chondrodysplasia Punctata

Form

Genetics

Key features

Rhizomelic CDP (RCDP1-5)

Autosomal recessive peroxisomal: PEX7, GNPAT, AGPS, FAR1, PEX5L

A spectrum graded by residual plasmalogen - classic: symmetric rhizomelia, delay, cataracts, early death; nonclassic: milder, better growth and cognition

Conradi-Hunermann (CDPX2)

X-linked dominant (EBP); mostly females

Asymmetric limb shortening (discrepancy), scoliosis, ichthyosis, cataracts; milder

X-linked recessive (CDPX1)

ARSL/arylsulfatase

Brachytelephalangic - nasal + distal-phalangeal hypoplasia

Teratogenic/secondary

Warfarin embryopathy; maternal autoimmune (SLE)

Phenocopy of CDP - take maternal history

Evidence

Skeletal dysplasias of the fetus and infant (including chondrodysplasia punctata)

Jezova M, Pavlovska D, Grochova I, Michenkova A, Vlasin P • Ceskoslovenska Patologie (2023)

Key Findings:

More than 400 genetic skeletal disorders are included in the latest classification; the most severe/lethal phenotypes are identifiable in the prenatal period, and perinatal autopsy/post-mortem radiographs are crucial for definitive diagnosis.
Chondrodysplasia punctata is among the recognised skeletal dysplasias encountered in fetal/neonatal practice (alongside thanatophoric dysplasia, osteogenesis imperfecta, campomelic dysplasia and achondroplasia).
An increasing number of cases are confirmed by genetic testing, reflecting the heterogeneous genetic basis of these dysplasias.

Clinical implication: CDP is a recognised fetal/neonatal skeletal dysplasia in which post-mortem radiographs and genetic testing secure the diagnosis - relevant to counselling and recurrence risk.

Verify on PubMed (PMID 37468326)