Syndromes

Question 1

Autosomal Dominant Polycystic Kidney Disorder

1. genetics
2. frequency
3. clin manifestation
4. diagnosis
5. treatment

Answer 1

1. AD - Polycystin 1 Polycystin 2
2. the most common hereditary human kidney disease, with an incidence of 1/400 to 1/1,000
3. cysts anywhere, inc. bowman capsule, renomegaly, Collecting duct dilation ESRD, liver cysts, Caroli Disease, cerebral aneurysms, hypertension, mitral valve prolapse, kidney stones, UTIs. ADPKD is a multiorgan disorder affecting many tissue types. Cysts may be asymptomatic but present within the liver, pancreas, spleen, and ovaries and when present help confirm the diagnosis in childhood. Intracranial aneurysms,
4. DPKD is confirmed by the presence of enlarged kidneys with bilat- eral macrocysts in a patient with an affected 1st-degree relative. ddx: The differential diagnosis includes renal cysts associated with glo- merulocystic kidney disease, tuberous sclerosis, and von Hippel- Lindau disease, which may be inherited in an autosomal dominant pattern
5. reatment of ADPKD is primarily supportive. Control of blood pres- sure is critical

Question 2

Autosomal Recessive Polycystic Kidney Disorder

1. genetics
2. frequency
3. clin manifestation
4. diagnosis
5. treatment

Answer 2

1. AR: Fibrocystin/ polyductin PDHD1
3. First yr of life; perinatal onset, cysts in Distal nephron, CD. Also assoc with hepatic fibrosis, pulm hypoplasia, hypertension

Question 3

Nephronophthisis

Answer 3

1. AR, Nephrocystins (NPHP1-9), ciliary dysfunction
3. cysts in medullary DCT, Retinal degeneration; neurologic, skeletal, hepatic, cardiac malformations

Question 4

tuberus Sclerosis

Answer 4

1. AD: Tuberin (TSC1), Hamartin (TSC2)
3. tubers and cysts in the loope of henle, DCT. Renal cell carcinoma Tubers, seizures Angiomyolipoma Hypertension

Question 5

Von Hippel Lindau syndrome

Answer 5

1. AD - VHL protein
3. cysts in the cortical nephrons, Retinal angioma, CNS hemangioblastoma, renal cell carcinoma, pheochromocytoma

Question 6

Oral-Facial-Digital syndrome

Answer 6

1. X-D, OFD1
3. cysts in the glomeruli, Malformation of the face, oral cavity, and digits; liver cysts; mental retardation

Question 7

Bardet-Biedel syndrome

Answer 7

1. AR - BBS14
3. cysts in the renal calyces,, Syndactyly and polydactyly, obesity, retinal dystrophy, male hypogenitalism, hypertension, mental retardation.

Question 8

Joubert syndrome and related disorders

Answer 8

1. AR, JBTS1 - JBTS20
3. cystic dysplasia, NPHP

Question 9

Meckel-Gruber syndrome

Answer 9

1. AR - MKs1-MKS10

Question 10

Zelwegger Syndrome

Answer 10

1. PEX1-3, 6-10, 11, 13, 14, 16, 19, 26
3. Intrahepatic biliary dysgenesis

Question 11

Cartilage-hair syndrome

Answer 11

Cartilage hair hypoplasia is a genetic disorder that affects the metaphyseal area of the long bone — the wider part at the end — causing lower-extremity abnormalities. The condition is an autosomal recessive disorder, meaning it is passed on to a child by both parents. The defect is caused by a problem with the spherical or rod-shaped parts of a cell called mitochondria.
Cartilage-hair hypoplasia is an autosomal recessive disorder where children have immunodeficiency, short limbed dwarfism and sparse, fine hair

Question 12

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome:

Answer 12

ICF syndrome is a rare disorder characterized by immune defects (primarily B cell development), facial anomalies and profound genomic instability involving the centromeric regions of chromosomes 1, 9 and 16.

Question 13

P14 deficiency

Answer 13

• Oculocutaneous hypopigmentation
• Short stature
• Coarse facial features
• Severe neutropenia ANC < 500
• Defective cytotoxic T cell function
• Humoral immunodeficiency - reduced switched memory B cell numbers, low IgM, and low IgG (during adolescence) have been reported. Impaired vaccine responses have also been observed.
• Moderate bleeding disorder - Prolonged bleeding time occurs due to defects in platelet aggregation.

Question 14

Griscelli syndrome
Griscelli syndrome type 1 involves severe problems with brain function in addition to the distinctive skin and hair coloring. Affected individuals typically have delayed development, intellectual disability, seizures, weak muscle tone (hypotonia), and eye and vision abnormalities.

Answer 14

type 1: is an inherited condition characterized by unusually light (hypopigmented) skin and light silvery-gray hair starting in infancy. Researchers have identified three types of this disorder, which are distinguished by their genetic cause and pattern of signs and symptoms.
type 2:
They also develop an immune condition called hemophagocytic lymphohistiocytosis (HLH), in which the immune system produces too many activated immune cells called T-lymphocytes and macrophages (histiocytes)

Question 15

Chediak-Higashi

syndrome

Answer 15

also presents with partial oculocutaneous albinism and immunodeficiency but not the mentioned hair findings. Giant cytoplasmic granules in leukocytes and platelets is pathognomonic for Chediak-Higashi syndrome. Microscopy of blood film would not be normal.

Question 16

Schimke-immuno-osseous-dysplasia

Answer 16

Most affected individuals have distinctive physical features. These include fine hair (60%), a thin upper lip, a broad, low nasal bridge (68%), a bulbous nasal tip (83%), and disproportionately short stature (98%). Additional features include excessive inward curvature of the lumbar spine (lumbar lordosis, 84%), a protruding abdomen, and hyperpigmented macules (85%) on the trunk and occasionally on the neck, face, arms and legs. Less common physical features include absent or small teeth and corneal opacities (19%).
Growth failure:t he short stature arises generally because of spondyloepiphyseal dysplasia (86%), a disorder of skeletal growth; 
Renal failure: The kidney disease is characterized by progressively worsening loss of protein in the urine and ultimately concludes with renal failure.
Endocrine abnormalities (thyroid)

Question 17

Roifman syndrome

Answer 17

is a rare autosomal recessive disorder characterized by growth retardation, spondyloepiphyseal dysplasia, cognitive delay, facial dysmorphism, and antibody deficiency

Question 18

Bloom syndrome

Answer 18

is an inherited disorder characterized by short stature, a skin rash that develops after exposure to the sun, and a greatly increased risk of cancer.This scenario describes Bloom syndrome, an autosomal recessive disorder which has increased risk of malignancy. Children have a characteristic appearance and develop an erythematous photosensitive rash in the first two years of life. Bloom syndrome is a rare disorder but especially prevalent among the Ashkenazi Jewish population. Although it is rare, it is common in exams.

Question 19

Nijmegen breakage syndrome (NBS)

Answer 19

NBS is caused by mutations in the nibrin (NBN) gene on 8q21 that encodes the protein nibrin. Patients have progressive, severe microcephaly. They also have intrauterine growth retardation and short stature, immunodeficiency with recurrent sinopulmonary infections and are susceptible to developing lymphomas. Radiation sensitivity is also a feature of ataxia telangiectasia but you would not expect severe microcephaly. You would also expect ataxia and nystagmus.

Question 20

CD40 ligand deficiency

Answer 20

is also known as Hyper IgM and is known to be associated with cryptosporidium infection. Chronic infection and inflammation can lead to cholangiocarcinoma. They are also susceptible to peripheral neuroectodermal tumours of the gastrointestinal tract. All of the options are immunodeficiency disorders that have increased risk of malignancy but CD40 ligand deficiency is particularly at risk of cholangiocarcinoma.

Question 21

IPEX - FOXp3 (master regulator of Treg lineage)

Answer 21

A serious course of the disease is marked by a triad of symptoms: intractable diarrhea, T1DM, ecezema.
he most representative criterion for diagnose of IPEX syndrome is autoimmune enteropathy. First symptoms of enteropathy begin in first day of life and they are characterized by diarrhea, vomiting, gastritis, ileus and colitis. The second hallmark is type 1 diabetes (T1D) and the worst complication of it is destruction of pancreas confirmed by histological examinations. Dermatitis is next sign and it can be presented in three forms: eczematiform (mainly atopic dermatitis), ichthyosiform and psoriasiform or combinations of them. Other skin manifestations can include cheilitis, onychodystrophy and alopecia. Beside the three most significant triada of symptoms during this syndrom other not so typical symptoms include: thyroid and renal dysfunction, reduced counts of thrombocytes and neutrophils, arthritis, splenomegaly, lymphadenopathy and infection
Treatment
• TPN (nutritional purpose)
• Cyclosporin A and FK506
• Sirolimus (should FK506 prove non-effective)
• Granulocyte colony stimulating factor
• Bone marrow transplant
Rituximab (anti IL6

Question 22

Fanconi Anaemia

Answer 22

Genetic defect: Autosomal recessive condition with mutatiosn in both copies of the DNA repair genes (sucseptibility to csncer)
Diagnostic test: chromosome breakage studies
Genetic testing: Exome with Fanconi genes analysed or Fanconi gene panel

Congenital anomalies: short stature & microcephaly, developmental delay
- Abnormal thumb/radius (radial ray), renal anomalies, GI atresias
- Hyper/hypopigmentation: freckles, CAL patches
Bone marrow failure
- Pancytopenia (may not be all cell lines at presentation)
- Typically 1st decade (5 yo)

Question 23

Kearns-Sayre syndrome

Answer 23

Mitochondrial encephalomyopathy: mitochondrial deletion - heart block, opthalmoplegia, retinopathy, CSF protein, cerebellar signs

not maternally inherited,. deletions or duplications of mtDNA that reflect altered communication between the nucleus and the mitochondria