Albright syndrome

Albright syndrome: A genetic disorder of bones, skin pigmentation and hormonal problems with premature sexual development. Also called McCune-Albright syndrome and polyostotic fibrous dysplasia. Albright syndrome (McCune¾Albright syndrome) Consists of polyostotic fibrous dysplasia (multiple bones affected), patchy skin pigmentation (referred to as cafe-au-lait spots), and an endocrine abnormality (usually precocious puberty in girls). Facial asymmetry affects up to 25% of cases.

What gene mutation cause mc Cune Albright’s syndrome?

McCune-Albright syndrome is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.

In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions by regulating the activity of hormones. The protein produced from the GNAS gene helps stimulate the activity of an enzyme called adenylate cyclase. GNAS gene mutations that cause McCune-Albright syndrome result in a G protein that causes the adenylate cyclase enzyme to be constantly turned on (constitutively activated). Constitutive activation of the adenylate cyclase enzyme leads to over-production of several hormones, resulting in the signs and symptoms of McCune-Albright syndrome.

Cleidocranial Dysostosis (Cleidocranial Dysplasia)

Cleidocranial dysostosis (cleidocranial dysplasia) is an autosomal dominant inherited condition consisting of hypoplasia or aplasia of the clavicles, delayed ossification of the cranial fontanelles, and a large, short skull. Associated features are shortness of stature, frontal and parietal bossing, failure to pneumatize the air sinuses, a high arched palate and/or clefting, mid-face hypoplasia, and failure of tooth eruption with multiple supernumerary teeth. Many of the teeth present have inherent abnormalities such as dilaceration of roots or crown gemination. Hypoplasia of secondary cementum may occur. The condition mainly, though NOT exclusively, affects membraneous bone.

Affected individuals may be 3 to 6 inches shorter than other members of their family, and may have:

• short, tapered fingers and broad thumbs;
• short forearms;
• flat feet;
• knock knees; and
• an abnormal curvature of the spine (scoliosis).

Characteristic facial features may include:

1. a wide, short skull (brachycephaly);
2. a prominent forehead;
3. wide-set eyes (hypertelorism); a
4. flat nose; and a
5. small upper jaw.

Dental abnormalities seen in cleidocranial dysplasia may include:

• delayed loss of the primary (baby) teeth;
• delayed appearance of the secondary (adult) teeth;
• unusually shaped, peg-like teeth;
• misalignment of the teeth and jaws (malocclusion); and
• extra teeth, sometimes accompanied by cysts in the gums.

Genes related to Cledocranial Dysplasia

It is transmitted as an autosomal dominant trait. CCD is caused by mutation in the RunX2 gene on Chromosome 6p21.

The RUNX2 gene provides instructions for making a protein that is involved in bone and cartilage development and maintenance. This protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the RUNX2 protein acts as a "master switch," regulating a number of other genes involved in the development of cells that build bones (osteoblasts).

Some mutations change one protein building block (amino acid) in the RUNX2 protein.

Above mutations may cause..

· Delayed closure (ossification) of the space between the bones of the skull (fontanels)

· Premature closing of the coronal suture

• · Protruding jaw (mandible) and protruding brow bone (frontal bossing)
• · Wide nasal bridge due to increased space between the eyes (hypertelorism)
• · High arched palate or possible cleft palate
• · Short stature
• · Scoliosis of the spine

Problems which child would have

· Dental abnormalities - failure to lose the baby teeth (deciduous) at the expected time; slow eruption of secondary teeth; extra teeth; delayed or absent formation of teeth

• · Ability to touch the shoulders together in front of the body
• · Wide pelvic bone
• · Loose joints
• · Hearing loss and/or frequent infections

Patient With Urinary Symptoms

The presence of disease in urinary tract may be detected because of

• 1. Presentation with a symptom or clinical sign that indicates an underlying renal disorder

• 2. The presence of a systemic disease known to involve the kidney

• 3. The finding of asymptomatic urinary abnormalities or disordered renal function tests

Symptoms of renal disease include

• Disturbance in the act of micturition

• Alteration in the amount and appearance of urine

• Pain : renal, ureteric, vesical, and urethral

• General symptoms of renal disease

• Disturbance in the act of micturition

1.Frequency - Passing urine more often than usual without increase in the amount of urine

Results from..

Irritation of the bladder

Reduction in the capacity of the bladder

Pressure from a pelvic tumour

• Disturbance in the act of micturition

2. Dysuria - Pain experienced prior to, during, or following micturition usually in the urethra or suprapubic region

Usually results from disease of the..

Bladder

Prostate

Urethra

• Disturbance in the act of micturition

3.Retention of urine

Occurs in

Obstructive lesions of the urethra

Disease of the spinal cord

Coma

• Disturbance in the act of micturition

4.Nocturia - Passing urine in the night (commonly associated with polyuria)

Other causes

Diabetes mellitus

Prostatism

Cystitis

Bladder tumours

• Disturbance in the act of micturition

5. Incontinence of urine

Seen in

Cerebrovascular lesions

Paraplegia

Multiple slerosis

Prolapsed uterus with cystocele

• Disturbance in the act of micturition

6. Hesitancy –

Delay in initiating the urine flow usually seen in males with prostatism

• Alteration in the amount of urine

Polyuria - over 3000 ml per day

Oliguria - less than 300 ml per day

Anuria - neglible urine output

• Alteration in the amount of urine

Causes of polyuria

1.Diabetes Mellitus

2.Diabetes Insipidus

3.Psychogenic polydipsia

4.Chronic renal failure

5.Hypokalemia

6.Hypercalcemia

• Alteration in the amount of urine

Oliguria –

Seen in acute renal failure

Pre renal failure – Shock

Haemorrhage

Dehydration

Cardiac failure

Intrinsic renal failure –

Acute glomerulonephritis

Acute tubular necrosis

• Alteration in the amount of urine

Anuria –

Must be differentiated from retention of urine

Causes include

Infarction of a kidney or both kidneys

Bilateral cortical necrosis

Complete obstruction of both ureters

• Alteration in the appearance of urine

1. Haematuria –

Red or smoky brown colour

• Alteration in the appearance of urine

• Causes of haematuria

Painless – Urinary tract obstrution

Tuberculosis

Urogenital tumors

Glomerulonephritis

Renal cystic disease

Painful – Renal calculi

Urinary tract infection

Reflux nephropathy

Renal papillary necrosis

Renal infarction

• Alteration in the appearance of urine

2. Blackish or coca cola in colour due to haemoglobinuria and myoglobinuria

• Alteration in the appearance of urine

3.Frothy urine –

Commonly due to proteinuria

• Alteration in the appearance of urine

Proteinuria

A small amount of protein (usually less than 100 mg) is normally excreted in the urine daily in healthy people

• Proteinuria

Significant proteinuria

Physiological

Pathological

• Proteinuria

Physiological

(Proteinuria less than 1000 mg / L)

Transient Proteinuria without renal damage seen in

Cold exposure

Vigorous exercise

Febrile illness

Congestive cardiac failure

• Proteinuria

Pathological proteinuria

Proteinuria more than 1000 mg / L

Commonly seen in

Glomerular disease

Tubular disease

Amount is very small or no proteinuria in some renal diseases

Polycystic kidney disease

Renal scarring

Obstructive uropathy

• Alteration in the appearance of urine

Urine become turbid with

Infection

Precipitated urates

Precipitated phosphates

• Alteration in the appearance of urine

Drugs causing discolouration of urine

Tetracycline yellow

Desferrioxamine reddish brown

Phenindione pink

Nitrofurantoin brown

Rifampicin- red

Methylene blue green

Methyl dopa grey

Metronidazole darkening of urine

Pain – as a manifestation of renal disease

Burning sensation or discomfort over suprapubic region – Cystitis

Perineal pain or rectal pain – Prostatitis

Pain felt in the flank, hypochondrium or iliac fossa – Renal pain

Pain – as a manifestation of renal disease

Acute obstruction of ureters due to stone or blood clot – Colicky pain radiates from loin to groin and to the testicle in the male

Chronic obstruction – less severe pain and sometimes no pain

Enlarged kidneys – dull, nagging or flank pain

Acute glomerulonephritis – typically painless

• General symptoms and signs of renal disease

1.Fever - Urinary tract infection may be associated with renal abnormality

2.Dyspnoea

Fluid overload in renal impairment

Metabolic acidosis in renal impairment

Pleural effusion in nephrotic syndrome

• General symptoms and signs of renal disease

3.Oedema (facial and dependent)

chronic kidney disease

nephrotic syndrome

4.Pruritus – in chronic kidney disease

5.Distal brown discolouration of nails – in chronic kidney disease

• General symptoms and signs of renal disease

• 6.Pallor – in chronic kidney disease

• 7.Hyperpigmentation - in chronic kidney disease

• General symptoms and signs of renal disease

8.Symptoms of ureamia

Anorexia

Lethargy

Nausea

Poor sleep

Poor concentration

Itching

Restless legs

Barium anemia of bowel