Malformations, syndromes and diseases

Histology

Connective tissue

- osteogenesis imperfecta: (collagen defect) autosomal dominant mutation of collagen

genes (COL1A1 or COL1A2). It results in bones that break easily (*1)

- Kniest displasia: is a disorder of bone growth characterized by short stature (dwarfism)

with other skeletal abnormalities and problems with vision and hearing. it is caused by

mutations in the COL2A1 gene. This gene provides instructions for making a protein that

forms type II collagen.

- Ehlers-Danaos syndrome: is a group of genetic connective tissue disordersIt may be

caused by Mutations in the following genes: Fibrous proteins: COL1A1, COL1A2,

COL3A1, COL5A1, COL5A2, and TNXB Enzymes: ADAMTS2, PLOD1, B4GALT7, DSE,

and D4ST1/CHST14. Symptoms can vary from mildly loose joints to life-threatening

complications such as aortic dissection. Chronic pain or early osteoarthritis may also

occur.

- Marfan’s syndrome: leads to a severe arterial impairment and high-risk of aortic

aneurysm, is due to fibrillin genetic anomaly

Bone

- osteogenesis imperfecta: Genetic disorder with defective collagen production lead to

fragile bone (*1)

- Osteomalacia: (mineralization defect) softening of the bones due to a lack of vitamin D

or a problem with the body's ability to break down and use this vitamin. This result in

defective meneralization and bone softening.

- Osteoporosis: osteoclasts are more active then osteoblasts, resulting in a decrease of

bone mass, with normal bone mineralization and microstructure

- Paget disease: chronic disorder that can result in enlarged and misshapen bones.

Paget's is caused by the excessive breakdown and formation of bone, followed by

disorganized bone remodeling. This causes affected bone to weaken, resulting in pain,

misshapen bones, fractures,and arthritis in the joints near the affected bones.

Blood

Red blood cell (RBC) disorder

- Anemias: low oxygen transport capacity of the blood, red blood cell low count or

hemoglobin deficiency:

Aplastic Anemia

- inability of the bone marrow to produce blood cells

- Blood loss Anemia

- Hemolytic anemia

- Pernicious Anemia

- Impaired vitamin B12, absorption 1

- Iron deficiency anemia

- Blood loss

- RBC small and lighter color

- Microcytosis/Macrocytosis: dimension

- Anisocytosis: different dimension

- Poikilocytosis: abnormally shaped

- Howell–Jolly bodies: basophilic nuclear remnants

Membrane defects

- Cytockeleton protein defects : ankyrin, spectrin, protein 4.1, protein 4.2

- Membrane defect: band 3.

- Spherocytosis: Loss of connection between membrane and cytoskeleton

- Elliptocytosis: RBC are elliptical. Many defects can results in elliptocytosis It is a

disease related to the impaired ability of erythrocyte to get back to original shape after

transit in small capillaries. Hemolysis is well compensated. MCV is not reduced, MCHC

is not increased. NO reduced osmotic resistance. Often there is no need of therapy. In

few cases splenectomy is sufficient

- Ovalocytosis: RBC are elliptical.

- Stomatocytosis Permeability disorder (protein 7.2). Reduced MCHC And increased

MCV. Hemolysis is well compensated. Reduced osmotic resistance. Often there is no

need of therapy.

- Hereditary spherocytosis: binding between ankyrin and spectrin is impaired.

- Loss of connection between cytoskeleton and membrane

- lipids loss, surface reduction and spheroids shape

- Erythrocyte blocked in splenic capillaries.

- Chronic hemolysis.

- reduced erythrocytes survival

Drepanocytosis (Sickle-cell

- disease): Mutation that affect hemoglobin solubility

Classic point mutation desease Glu--> Val

β6

(HBS)

Sickle-cell disease

NB Glu-->Lys results in less severe HBS.

β6 2

Neutrophilia: •Physiologic

. Stress, exercise

Infection

• Infilamation/tissue necrosis

– tumors, trauma, dermatitis

• Drugs

• Steroids, epinephrine, digitalis, eparin

• Metabolic

– Diabetic acidosis, gout, hyperthyroidism, uremia

- Neutropenia: Bone marrow failure

Stop in the maturation process

– Bone marrow disorder

• aplastic Anemia, vit b12 deficiency, chemioterapy, benzene,

EtOH, radiation

– Reaction to some drugs

• Chloramphenicol, PCNS, sulfonamides, diuretics, hypoglycemic.

– Bone marrow transplant

– Hereditary defect

• Fanconi Anemia, Kostmann syndrome

•

- Eosinophilia: Neoplasia

• Allerergic reactions, parasites

- •

Eosinopenia: Stress

• Infections

• Steroids/Cushing syndrome

•

Basophilia:

- Hypersensitivity reaction

• Allergy, asma, eczema

• Hypothyroidism

•

Basopenia Stress Infections

- • Steroids/ Cushing syndrome

• Ulcerative colitis 3

Embryology

Gametogenesis, fertilisation, 1st, 2sd and 3rd week

- Sperm defects: giant, micro sperm, double head, double body, long head, rough head,

abnormal middle piece

- hydatidiform moles: complete hydatidifom mole is a pregnancy without an embryo. In a

partial hydatidiform mole some embryonic structures develop

Heart

- cardia bifida: when the two endocardial tubes fail fusing, and two tube-lobe structures

form rather than a single primary heart tube, and continue to undergo cardiogenesis

- atria septa defects (ASD) (acyanotic)

-> perforations of the septum primum

-> short septum primum

-> large oval foramen

-> abnormally large foramen ovale and very short septum primum

-> patent septum primum (hight atrial septa defect)

- ventricular septal defects (acyanotic)

- Persistent truncus arteriosus: no division outflow tract occurs

- Tetralogy of Fallot (cyanotic) involves 4 heart defects . a large ventricular septa defect

. pulmonary artery stenosis

. right ventricular hypertrophy

. an overriding aorta

- Transposition of great arteries: tricuspid valve connects right ventricle with left atrium,

mitral valve connects left ventricle with right atrium

- Di George Syndrome: deletion of 22q11 characterized by a pattern of malformations that

have their origin in abnormal neural crest development. The children have facial defects,

thyme hypoplasia, parathyroid dysfunction, cardiac abnormalities like a persistent trunks

arterioles and tetralogy of Fallot

4. Muscoloskeletal system

- meningocoele: protrusion that consists solely of membranes

- menincomiocoele: protrusion thet includes an intact spinal cord

- anancephaly: no neurocranium

- microcephaly: no brain development

- spina bifida - > occulta (it is covered by the skin)

- > with meningocoele

- > with meningomyelocele

- > with myeloschisis (if the sac breaks)

- scoliosis - > wedge vertebrae (partial unilateral failure of formation)

- > hemivertebra ( complete unilateral failure of formation)

- > congenital bar (unilateral failure of segmentation)

- > block vertebra ( bilateral failure of segmentation) 4

- Syndactyly: fusion of one

ore more fingers or toes

(lobster claw hand)

- polydactyly: more fingers

and toes

- amelia: complete

absence of one or more

extremities

- meromelia: partial

absence of one or more

extremities

- lobster claw hand

Urinary system

- oligohydramnios: fetuses

who do not have enough amniotic fluid

- bilateral renal agenesis: fetuses with total absence of both kidneys

- Potter sequence: Autosomal recessive polycystic kidney disease with anomalies caused

by oligohydramnios such as flat face, limb contractures, low-set ears, and dry wrinkled

skin

- Multicystic dysplastic kidney: autosomal dominant polycystic kidney disease

- Duplication of the ureter

- one ureter opens into the bladder, and the other is ectopic

- pelvic kidney: when a kidney completely fails to relocate

- horseshoe kidney: when the inferior poles of the two metanephroi fuse together during

relocation, forming a U-shaped horseshoe kidney, and got caught under the inferior

mesenteric artery, and therefore does not reach its normal site

- accessory renal arteries: when on or ore of the transient inferior renal arteries fail to

regress

Bladder defects:

- urachal fistula: may cause urine t drain from the umbilicus

- urachal cyst: if only a part of the allantois persist, results in a cystic dilation

- urachal sinus: when the lumen in the upper part persists

- exstrophy of the bladder: is a ventral wall body defect in which the bladder mucosa is

exposed outside. Rare anomaly

- exstrophy of the cloaca: is a more severe ventral wall body defect in which migration of

mesoderm is inhibited and the tail (caudal) fold fails to progress. This defect is

associated with an early amniotic rupture, and involves also spinal defects with or

without meningomyelocele, imperforate anus, and usually omphalocele

Genital system

Duplications of the uterus

- uterus didelphys 5

- uterus arcuatus

- uterus bicornis

- atresia of cervix

- atresia of vagina

Defects in the Male Genitalia

Hypospadias: abnormal urethral orifices, resulted from failure of fusion of the urethral

• folds

• Epispadias: defect on the ventral wall combined with the exstrophy of the bladder

• Exstrophy of the bladder

• Micropenis

• Bifid penis or double penis

cryptorchidism: undescended testes

•

Digestive system

- anular pancreas: when two lobes of a bilobed ventral pancreatic bud migrate in opposite

directions around the duodenum to fuse with the dorsal pancreatic bud, forming a

complete ring encircling the duodenum. This condition may compress the duodenum

and cause gastrointestinal obstruction (duodenal stenosis)

- congenital omphalocele: persistence of the herniation of the abdominal contents into the

proximal part of the umbilical cord (about 1/5000 births). The abdominal cavity is

relatively small when there is an omphalocele, immediate surgical repair is required.

Omphalocele results of failure of the intestines to return to the abdominal cavity. The

covering of the hernial sac is the epithelium of the umbilical cord, which s a derivative of

the amnion

- umbilical hernia: when the intestines return back to the abdominal cavity during the 10th

week and then herniate through an imperfectly closed umbilicus (DIFFERENT from

omphalocele). The protruding mass is covered by subcutaneous tissue and skin. The

hernia reaches its maximum size at the end of the first month after birth

- Meckel diverticulum: one of the most abnormalities in the digestive tract, 2 to 4% of

people, it sometimes becomes inflamed and mimics the symptoms of an appendicitis.

- congenital megacolon: a part of the colon is dilated because of the absence of

autonomic ganglion cells in the myenteric plexus distal to the dilated segment of colon.

The dilation results from failure of peristalsis in the ganglionic segment. In most cases

only rectum and sigmoid colon are involved. I