Miscellaneous syndromes: Autosomal Recessive

Question 1

Familial Dysautonomia (Hereditary Sensory and Autonomic Neuropathy (HSAN) Type III)

Answer 1

Inheritance: Autosomal recessive
Gene: IKBKAP
● AJ founder mutation c.2204+6T>C
● Only three mutations total

Question 2

Familial Dysautonomia (Hereditary Sensory and Autonomic Neuropathy (HSAN) Type III) 
Major features

Answer 2

Major features
●Progressive neuronal deterioration
●Usually normal intellect
●Inability to produce tears
●Delayed speech, delayed motor milestones
●Unsteady gait
●Corneal abrasion
●Decreased pain and temperature perception
●Poor growth
●Dysphagia
●Skin picking/ self mutilation
●Unstable blood pressure
●Red, puffy hands
●Dysautonomia crises
    oVomiting, increased heart rate, increased blood pressure, sweating, drooling, blotching of skin, negative change in personality
   oResponse to physical and emotional stressors

Question 3

Familial Mediterranean Fever: Genetics

Answer 3

Inheritance: Autosomal recessive
Gene: MEFV

Question 4

Familial Mediterranean Fever: Features

Answer 4

●Autoinflammatory disease
●AA Amyloidosis
●Recurrent febrile episodes with peritonitis, synovitis, and/or pleuritis
●Recurrent erythema
●Elevated serum fibrinogen
●Kidney failure may occur from prolonged amyloidosis

Treatment:
●Preventative oral colchecine

Question 5

Fryns Syndrome: Genetics

Answer 5

Inheritance: Autosomal recessive
Genes: Unknown, may be associated with genes on chromosome 8 and/or 15

Question 6

Fryns Syndrome: Major features

Answer 6

●Diaphragmatic hernia
●Distal digital hypoplasia
●Significant pulmonary hypoplasia
●Death in the neonatal period
●Dysmorphic features
   oCoarse facial features
   oOcular hypertelorism
   oBroad, flat nasal bridge
   oLong philtrum
   oLow-set and poorly formed ears
   oMacrostomia
   oMicrognathia
●Characteristic associated anomalies

Question 7

Fryns Syndrome: characteristic associated anomalies:

Answer 7

oPolyhydramnios
oCloudy corneas/microphthalmia
oOrofacial clefting
oBrain malformation
oCardiovascular malformation
oRenal dysplasia
oRenal cortical cysts
oGI malformation
oGenital malformation

Chromosome studies should be done to rule out other causes of diaphragmatic hernia

Question 8

Pendred Syndrome: Genetics

Answer 8

Inheritance: Autosomal recessive
Gene: PDS

Question 9

Pendred Syndrome:Major features

Answer 9

●Congenital bilateral sensorineural hearing loss
oCaused by enlarged vestibular aqueducts (always think Pendred if you see this)
oHead trauma can rupture the aqueducts and worsen the severity of hearing loss
●Thyroid dysfunction
oHypothyroidism
oGoiter
●Allelic disorder – enlarged vestibular aqueduct syndrome

Question 10

Pseudoxanthoma Elasticum (PXE): Genetics

Answer 10

Inheritance: Autosomal recessive
Gene: ABCC6

Question 11

Pseudoxanthoma Elasticum (PXE): Major Features

Answer 11

●Pseudoxanthomas in the eyes, skin, and blood vessels
oMineralization and fragmentation of elastic fibers in soft tissues
●Premature atherosclerosis
●Peau d’orange on ophthalmologic exam
●GI bleeding (usually stomach)
●Muscle pain
●Increased risk for MI

Question 12

TAR Syndrome (Thrombocytopenia with Absent Radius)

Answer 12

Inheritance: Autosomal recessive
Genes: A bunch

Major features:
●Thrombocytopenia
●Congenital absence of the radial bone
●Joint problems
●Heart anomalies
●Genitourinary anomalies

Question 13

Usher Syndrome

Answer 13

Inheritance: Autosomal recessive

Major features:
● Hearing loss (congenital in type I, hard of hearing in type II, progressive in type III)
● Retinitis pigmentosa and associated vision loss
● Vestibular abnormalities leading to balance issues

Question 14

Wolfram Syndrome

Answer 14

Inheritance: Autosomal recessive
Gene: WFS1

Major features:
●Childhood-onset diabetes mellitus
●Optic atrophy
●Deafness

Question 15

Cohen Syndrome: Genetics

Answer 15

Inheritance: Autosomal recessive
Gene: VPS13B (COH1)

Question 16

Cohen Syndrome: Major features

Answer 16

Major features:
●Retinal dystrophy
●Acquired microcephaly
●Progressive high myopia
●Intellectual disability
●Global developmental delay
●Hyptonia
●Joint hypermobility
●Short stature
●Truncal obesity
●Slender extremities
●Sociable disposition
●Neutropenia
●Dysmorphic features
     oThick hair/eyebrows
     oLong eyelashes
     oWave-shaped palpebral fissures
     oBulbous nasal tip
     oSmooth philtrum