Syndromes

Question 1

Difficulty hearing, menorrhagia, macrothrombocytopaenia

Answer 1

Konigsmark syndrome
- due to mutation in DIAPH1 gene on chromosome 5q31
- a/w macrothrombocytopaenia but often no clinical features of thrombocytopenia

Question 2

Mutation in DIAPH1 gene?

Answer 2

Konigsmark syndrome (chromosome 5q31)

Question 3

Progressive hearing loss and multiple presentations with recurrent fever, joint pain, conjunctivitis and urticarial rash

Answer 3

Muckle-Wells syndrome
- has overlap with familial cold auto inflammatory syndrome and NOMID/CINCA (neonatal onset multisystem inflammatory disease/chronic infantile neurological, cutaneous and articular syndrome)

Question 4

Sensorineural hearing loss, limited adduction of right eye

Answer 4

Duane syndrome
- eye signs can occur in isolation but 30# have extra-ocular problems such as SNHL
- may have a deep set eye, or narrowing of the palpebral fissure

Question 5

Bilateral non-progressive SNHL (severe and profound), goitre with occasional hypothyroidism, dilation of vestibular aqueduct bilaterally +/- cochlear hypoplasia

Answer 5

Pendred syndrome (AR)

Question 6

Congenital bilateral SNHL, retinitis pigmentosa leading to gradual visual loss, variable vestibular impairment

Answer 6

Usher syndrome (AR) - three subtypes depending on genes affected
Type I: MY07A, USH1C, CDH23, PCHD15, USH1G
Type II: USH2A, GPR98, WHRN
Type III: CLRN1

Question 7

Mutations in KCNE1 gene and KCNQ1 gene

Answer 7

Lange-Niele syndrome (AR)

Question 8

Abnormal ventricular depolarisation and long QT syndrome, congenital deafness

Answer 8

Lange-Niele syndrome
- congenital deafness due to abnormal endolymph production in the cochlea

Question 9

Combination of congenital central hypoventilation syndrome (CCHS) and Hirschsprung disease

Answer 9

Haddad syndrome
- CCHS means suboptimal response to hypoxia and hypercarbia (caution with swimming)

Question 10

Syndrome associated with “windswept” deformity

Answer 10

Pseudoachondroplasia - can have genu valgus, genu varum, or “windswept” deformity where one leg is turned out and the other is turned in

Question 11

6 month old with failure to thrive, history of foul oily stools, FBC shows significant neutropenia

Answer 11

Schwachman-Diamond syndrome
- biallelic defects in SBDS gene
- protein of this gene is involved in ribosome biogenesis and mitosis

Question 12

Biallelic defects in SBDS gene

Answer 12

Schwachman-Diamond syndrome

Question 13

Mutation in CHD7 gene

Answer 13

CHARGE syndrome

Question 14

Keyhole shaped abnormality of the eye, abnormal ear development, failed newborn hearing test?

Answer 14

CHARGE syndrome

Question 15

VACTERL association

Answer 15

Vertebral defects, Cardiac defects, Tracheo-oesophageal defects, Renal anomalies and Limb abnormalities

Question 16

22q11.1 deletion

Answer 16

DiGeorge/velocardiofacial syndrome
- cardiac defects, poor immune system function, cleft palate, hypocalcaemia and developmental delay

Question 17

Microdeletion syndrome of chromosome 16

Answer 17

Rubenstein-Taybi syndrome

Question 18

Short stature, moderate to severe ID, dysmorphism and broad thumbs/first toes

Answer 18

Rubenstein-Taybi syndrome
- microdeletion of chromosome 16

Question 19

Hereditary sensorineural hearing loss, no other abnormalities

Answer 19

Connexian 26 mutations (80% AR)

Question 20

SCN1A gene

Answer 20

Gene that makes sodium channels
Associated with Dravet syndrome

Question 21

DEPDC5 gene

Answer 21

Gene responsible for modulating mTOR pathway
Results in familial focal epilepsy

Question 21

KCNQ2 gene

Answer 21

Encodes a potassium channel
Common cause of benign familial neonatal epilepsy, but can also present with epileptic encephalopathy (i.e. can cause a spectrum of presentations)

Question 22

Delayed puberty, anosmia, pre-pubertal levels of LH, FSH and testosterone

Answer 22

Kallmann syndrome
- hypogonadotrophic hypogonadism and anosmia
- can also have micropenis, undescended testes, midline facial defects and congenital solitary kidney

Question 23

Peripheral precocious puberty with fibrous dysplasia of bone, cafe au lait macules

Answer 23

McCune-Albright syndrome
- cafe au lait macules (“coast of Maine”)

Question 24

Syndrome caused by somatic mutation in the G protein that stimulates cyclic AMP?

Answer 24

McCune-Albright syndrome