MUSCULOSKELETAL DISORDERS IN CHILDREN😊

MUSCULOSKELETAL DISORDERS IN CHILDREN

Duchene Muscular Dystrophy

Q. A 4-year-old boy presents with difficulty in climbing stairs. There is a family history of similar illness in the child's maternal uncle. The Child's CPK levels are 12,400 units/L. What is the probable diagnosis?

X-linked Recessive disorder

Mainly affects boys

Gene affected:

Dystrophin gene;

Largest genes found in humans +
it is present on ChrXp21.
Leads to ⛔ of calcium uniport in mitochondria

Mode of inheritance:

X-linked recessive inheritance.

If Dystrophin protein is

less or reduced

Called Becker's muscular dystrophy (milder variant)

totally absent

Duchenne muscular dystrophy
Progressive increase in muscle weakness

Dystrophy → progressive weakness

Clinical features of DMD

Progressive proximal muscle weakness i.e.,

weakness involving thigh muscles
arm muscles

Clinical signs in DMD

On examination:

Pseudohypertrophy of calf muscles is seen,

inverted bottle appearance
Hour glass appearance
brachioradialis

Valley sign positive:

It is a groove-like depressed area
in between pseudo hypertrophied deltoid and infraspinatus muscles.

Gower sign positive:

Due to weakness in hip joint muscles
If a child with DMD is asked to get up from a sitting position,
he will first take the help of a hand
put them on the ground
take support of his legs
slowly taking help from himself,
the child will get up.

Floppy muscles

Most children become Wheelchair bound at 10-12 years

Subsequently leads to death

M/c: Congestive Heart Failure

Investigations findings in muscular dystrophy

Serum CPK levels

(Normal - <160 U/L):

10,000 U/L.
This is often used as screening and first-line investigation.

Definitive diagnosis:

PCR for dystrophin gene

It can be done by multiplex PCR or MLPA

(Multiplex Ligation-dependent Probe Amplification).

Muscle biopsy is not done to diagnose, but if done

Chest X-ray:

Cardiomegaly.

Others not used:

EMG

CPK MM:

Elevated initially
Falsely normal once wheel chair bound

NOTE: Gower sign in 25 year old female

Dermatomyositis

Treatment of muscular dystrophy

Supportive care including

physiotherapy,
taking care of cardio-respiratory issues.

Corticosteroids:

They decrease the progression of the disease but
it can not cure the disease.
It will improve muscle strength and
prolong the ambulation.
Prednisolone or Deflazacort can be used.

Newer drugs of muscular dystrophy:

Anti-sense oligonucleotides.

Eteplirsen (51 exon-skipping drug).

Get up Lirsen

ㅤ	DMD	BMD
Mutation	Frameshift / Non-sense	In-frame mutation
Protein	Truncated dystrophin protein	Dystrophin protein quality affected
BMD	More severe	Less severe

Rickets

Definition

A disease of growing bones

defective mineralization of the bone matrix at the growth plate

in children before the fusion of epiphysis.

softening and weakening of bones

due to impaired mineralization.

Etiology of Rickets

The most common cause of Rickets is a nutritional deficiency of Vitamin D.

Nutritional Rickets

Vitamin D deficiency: Most common cause

Nutritional deficiency

(most common subset).

Congenital deficiency.
Inadequate dietary intake.
Malabsorption.
Liver/Kidney Disease.
Lack of sunlight exposure.
Drugs.

Calcium deficiency.

Phosphate deficiency.

Refractory Rickets

does not respond to the usual treatment

VDDR types I and II.

Chronic kidney disease (CKD):

Increased Phosphate

Renal tubular acidosis

Oncogenic/Tumor-induced

Vitamin D Resistant Rickets

↑↑ FGF 23 levels → ↑ renal phosphate wasting → ↓ Vitamin D

Congenital Hypophosphatemic Rickets

X Linked Dominant

PHEX gene

Mnemonic: Phex Phosphate FGF

Acquired Hypophosphatemic Rickets

Some benign mesenchymal tumors

Secrete FGF-23

Phosphaturia & hypophosphatemia.

Clinical Features of Rickets

General

Failure to thrive.

Protruded abdomen.

Listlessness.

Increased risk of respiratory infections:

softening of ribs,
impairs air movement during respiration.

Increased risk of fractures.

Delayed motor milestones.

Head and face

(Earliest) Craniotabes:

Due to softening of cranial bones;
also seen in

osteogenesis imperfecta,
congenital syphilis,
hydrocephalus,
and prematurity.

Large AF with delayed closure.

Wide sutures.

Frontal and parietal bossing.

Delayed dentition and dental caries.

Dental hypoplasia.

Chest

Rachitic rosary:

Beading of costochondral junctions.
(blunt and non-tender).
Note:

Scorbutic Rosary (in Scurvy)

sharp and tender

Harrison sulcus:

Due to the pulling of softened ribs by the diaphragm contraction.

Pigeon chest/Pectus Carinatum:

Prominent sternum.

Limbs

Only seen once the child starts weight-bearing.

Not seen in infants.

Swelling in wrist and ankle joints.

Wrist widening.

Double malleoli.

Coxa Vara:

Deformity of the proximal femur.

Genu varum or valgum deformity.

Bilateral genu varum:

Bowing of tibia.
Most common presentation.

Bilateral genu valgus (knock-knees).

Hypocalcaemia

Tetany.

Seizures.

Stridor.

Trousseau sign (more specific).

Sphygmomanometer → Carpopedal spasm
Accoucheur’s hand position

Chvostek sign.

Tapping facial nerve infront of tragus
Spasm of facial muscles

NOTE: Troisier’s sign

Left supraclavicular Lymphadenopathy
In metastatic abdominal lymphadenopathy

X ray Rickets

Radiological Features:

Genu valgum: Knees towards each other - Knock knees.
Bowing of the legs: Genu varum.

Metaphysis

Earliest

↓ Zone Provisional calcification - ZPC

Fraying, ragged edges → Irregular border
Cupping → Concavity
Splaying → Widening

Epiphysis

Widening → epiphyseal plates/growth plate.

Diaphysis

Bowing

Decreased density.

Healing Rickets: White Line of Frankel:

Mineralization of the growth plate appears as a dense line,

indicating healing.

Compared to a normal bone:

Investigations findings in Rickets

Serum Calcium:

(especially in early disease).
Normal or low.

Serum Phosphate:

Low.

PTH:

High.

Alkaline phosphatase:

High.

25(OH)VitD3:

Low (<10ng/ml or <30nmol/L)

(Normal: >20 ng/ml or >50 nmol/L).

Physiology of Vitamin D:

Vit D3 — (25 hydroxylase) —> 25-OH-Vit D3 — (1 alpha hydroxylase) —> 1, 25, (OH)2 VitD3 (Active form of Vit D).

PTH increases Ca & P absorption.

1, 25, (OH)2 VitD3 has feedback inhibition of PTH

Categories of Rickets based on investigations include:

Vitamin D Dependent Rickets

A/w endodermal dysplasia

VDDR Type 1

Vitamin D not converted to active form

VDDR Type 2

Active form cannot act on receptors

Scurvy

Mnemonic:

White (white line of frankel) Pelken (Pelken spur) Put in Glass (Ground glass) kuudu

Burgur (Whimberger) koduthu

Scorpion (scorbutic rosary) (Pencil thin cortex) caril kond poi

Step	Process	Key Points
1. Collagen backbone	Preprocollagen	Sequence: Glycine–Proline–Lysine (Polyproline α chain) (Glycine -X-Y)n → Left-handed turn ~1000 amino acids.
2. Hydroxylation	Hydroxylation of proline & lysine post-translational modification.	Both Requires Vitamin C → Deficiency causes Scurvy
3. Glycosylation	Glycosylation of hydroxylysine residues → form hydrogen and disulfide bonds.	Formation of procollagen → Triple helix structure (3α chains) → 3 chains twist together in right-handed direction. Defective process → osteogenesis imperfecta.

Extracellular Events:

Step	Process	Key Points
Proteolytic processing/ Cleavage of terminals	Cleavage of disulfide-rich terminal regions	form of tropocollagen.
Quarter staggered arrangement	Self-assemble Lateral arrangement of tropocollagen molecules.	form collagen fibrils
Cross-linking	Lysyl oxidase ► (requires Copper) Covalent cross-links for stability	Forms mature collagen; defects → Menkes disease

Vitamin C → Hydroxylation → Scurvy

Copper → for Crosslinking (Lysyl oxidase) → Maturation → Menkes

Barlow’s Disease (Infantile scurvy)

Age: 6–12 months (weaning period)

Needs Vitamin C supplementation

Q. A 1-year-old exclusively cow milk-fed boy presented with crying with touching of limbs, gum bleeding, and inability to move the right lower limb. What is the probable diagnosis?

Basic Defect

↓↓ Vit C ⇒ ↓↓ Hydroxylation of Lysine and Proline ⇒ ↓↓ Collagen 1

Defective collagen maturation of osteoid

(mineralization is normal).

Increased vascular fragility.

Factors

Humans cannot synthesize Vitamin C

due to lack of L-gulonolactone oxidase

Children predominantly fed on cow's milk.

Richest source of Vitamin C:

Amla / Indian gooseberry
Mnemonic: CAmala

History:

James Lind: Showed scurvy can be prevented by Citrus fruits

Daily requirement:

40 mg/day

Clinical Features

Bleeding gums.

Easy bruising.

Petechiae.

Cork screw hair follicles

Diagnosis

X-ray features of scurvy:

Scurvy → Comes with pain

Rickets → Painless

Subperiosteal hemorrhage.

most common

leading to bilateral knee pain
Painful pseudo paralysis.
Crying on touch.

NOTE: Scorbutic Rosary.

sharp & tender,
unlike rachitic rosary

Trummerfeld zone.

Seen adjacent to white line of Frankel.

Diaphysis:

Ground glass appearance.
Pencil thin outline cortex.

Metaphysis:

White Line of Frankel.

Helps differentiate from active rickets.
Seen in healing rickets.

Scorbutic Zone (Trümmerfeld zone):

Radiolucent band in the metaphysis.

Pelkan's Spur

Metaphysis forms a spur.

Epiphysis:

Wimberger Ring Sign:

ring shaped epiphysis
Ring appearance of epiphysis.
May be d/t bleeding

Differential Diagnosis (D/D) of Scurvy Radiological Findings

Healing rickets.

Congenital syphilis.

Plumbism (lead poisoning).

Leukemia.

Treatment

Vitamin C supplementation.

Marble Bone Disease / Albers-Schonberg disease

Q. An 11-month-old girl presented with pancytopenia and hepatosplenomegaly. An x-ray of her limbs showed the following picture. What is the diagnosis?

Pathophysiology

Defect in gene for carbonic anhydrase 2

Required by osteoclasts for acidification for bone resorption
Decreased osteoclast function (↓ Resorption).
Leads to increased bone formation (↑ Bone formation).
Erlenmeyer flask deformity

Resulting in the medullary cavity being obliterated by new bone,

↓↓ space for bone marrow.

Clinical Features

Excessive thickened bone.

Aplastic Anemia:

Due to marrow obliteration,

→ anemia, thrombocytopenia, and leucopenia.

Multiple infections (due to leukopenia).

Foramina are small

Cranial nerve palsies

X-ray

Bone within a bone appearance/ "Marble Bone Disease"

Increased density of the bone.
Mnemonic: Osteo Pettu → Bone vere bone nte ullil pettu

Rugger Jersey Spine

(also seen in Renal Osteodystrophy).

Dense, sclerotic bones.

Phocomelia

Thalidomide

Phocomelia (Proximal limb amputation)

Stillbirth

Q. A baby was born with the limb defects shown in the picture below. There is a history of thalidomide ingestion by the mother during her pregnancy. The probable diagnosis is?

Limbs resemble flippers of a seal.

Maternal intake of thalidomide during pregnancy is a risk factor.

Short proximal segments of limbs.

Osteogenesis Imperfecta

Q. A 15-month-old baby presented with multiple bony deformities and deafness. On enquiring, there was a recurrent history of limb fractures following trivial trauma in the child. On close examination, the child has a blue sclera. What is the probable diagnosis?

Important Information

The most common mode of inheritance in osteogenesis imperfecta:

AD.

genetically abnormal collagen (Type I collagen defect).

Leads to weak bones and recurrent pathological fractures.

Type 2 is most severe

Defects in COL1A1 or COL1A2
(type I collagen).

Clinical Features

Mnemonic: BITE

Bones = fractures
I = blue sclerae
Teeth = imperfections
Ear = hearing loss

Triad:

Blue sclera.

thin sclera → Choroid visible

Limb deformities due to recurrent fractures.

Deafness.

Easy bruising.

Multiple fractures in different stages of healing.

On antenatal scans.
Deformities

Delayed dentition.

Dental imperfections

(dentinogenesis imperfecta → opalescent teeth that wear easily due to lack of dentin)

Hearing loss (abnormal ossicles)

Labs

Normal lab values.

Treatment

Treat with bisphosphonates to ↓ fracture risk.

Pamidronate.

Mnemonic: Pavam koch → Pamidronate

NOTE:

Vander Hoeve Syndrome:

Osteogenesis Imperfecta.
Blue sclera.
Otosclerosis.
Pregnant() female on shorts (Schwartz sign) vandering (Vander) in Car (Carharts), Oto (Otosclerosis) van Van (Vander)- para (Paracusis willisii)vach - bcz avalde bone(Excessive bone deposition) poyi

JIA (Juvenile Idiopathic Arthritis)

JIA is similar to Rheumatoid arthritis → Difference:

JIA → Uveitis, < 16 years
RA → Scleritis, Episcleritis, Keratoconjuctivitis Sicca

Q. A 5-year-old girl presented with pain and swelling in the right knee for 3 months. There is also a history of pain in the right eye on and off. What is the diagnosis?

m/c in paediatric Anterior Uveitis

Extra

Cause enthesitis affecting Achilles tendon

Definition

Arthritis of >1 joint,

lasting for at least 6 weeks,
in a child < 16 years of age**.

Stills disease

ILAR CLASSIFICATION

Pauciarticular / Oligo articular: M/c type

Type I:

≤ 4 joints.
Associated with Uveitis/iridocyclitis
ANA positive Oligoarticular JIA (M/c)
Girls.
RF-

Type II:

Males

Poly articular:

>4 joints involved.

Systemic JIA:

Fever, rash hepatosplenomegaly.

Psoriatic arthritis

Enthesitis-related arthritis

Undifferentiated JIA

Treatment

Disease-modifying agents

weekly methotrexate.

In severe cases:

Steroids pulse therapy.

Uveitis A/w HLA B27 - associated arthritis = JRAP

Ankylosing Spondylitis

Psoriatic arthritis

Reiter's syndrome/Reactive arthritis.

JIA