Miscellaneous Syndrome: X linked Flashcards
Aarskog Syndrome (Aarskog-Scott, Faciogenital Dysplasia)
Inheritance: X-Linked recessive
Gene: FGD1
Aarskog Syndrome (Aarskog-Scott, Faciogenital Dysplasia): Featurea
Physical features:
●Hypertelorism ●Downslanting palpebral fissures ●Long philtrum ●Widow’s peak ●Mild-to-moderate short stature during childhood ●Brachydactyly ●5th clinodactyly ●Cutaneous syndactyly ●Single palmar crease ●Shawl scrotum ●Cryptorchidism ●Inguinal hernia ●Pectus deformities ●Webbed neck
Other features:
●Learning difficulties
●Intellectual disability (less common)
●Female “carriers” may be mildly affected
X-linked Agammaglobulinemia
Inheritance: X-linked recessive
Gene: BTK
X-linked Agammaglobulinemia: Features
Major features: ●Immune deficiency ●Recurrent bacterial infections ●Absence of circulating B cells ●Low serum immunoglobulins Treatment: ●Gammaglobulin supplementation ●Prophylactic antibiotics
Aicardi Syndrome
Inheritance: X-linked dominant
Gene: Unknown
Aicardi Syndrome: Features
Major features: ●Complete or partial absence of the corpus callosum ●Seizures (infantile spasms) ●Retinal lacunae ●Increased tumor risk ●Average lifespan 8-9 years
Alport Syndrome
Inheritance: Autosomal dominant, autosomal recessive, X-linked recessive
Genes: COL4A3, COL4A4, COL4A5
Alport Syndrome: Features
Major features: ●Onset of symptoms in early in childhood/young adult life ●Hematuria and proteinuria ●Glomerulonephritis ●End-stage kidney disease ●Progressive hearing loss ●Leiomyomatosis of the esophagus oDysphagia oVomiting oEpigastric pain ●Eye changes oCataracts oKerataconus oRetinal flecks in the macula ●Aortic dissection (rare) Treatment: ●ACE inhibitors slow progression of kidney disease ●Dialysis ●Kidney transplant
Coffin-Lowry Syndrome
Inheritance: X-linked
Gene: RPS6KA3
Coffin-Lowry Syndrome: Features
Major features: ●Short stature ●Severe intellectual disability ●Cardiac anomalies ●Auditory problems ●Dysmorphic features: oCoarse facies oFrontal bossing oHypertelorism oDownslanting palpebral fissures oBroad nose oFull, everted lips oPectus deformities oHypodontia oScoliosis/kyphosis oBrachydactyly oMicrognathia ●Female “carriers” may have intellect ranging from normal to severe intellectual disability and may have craniofacial anomalies ranging from mild to severe
Coffin-Siris Syndrome
Inheritance: Autosomal recessive, autosomal dominant
Genes: ARID1B, SOX11
Coffin-Siris Syndrome
Major features: ●Mild-to-severe ID ●Short thumbs with hyoplastic/absent nails ●Frequent respiratory infections ●Low birth weight/feeding difficulties ●Hypotonia ●Joint laxity ●Delayed bone age ●Microcephaly ●Coarse facial feat
Cornelia De Lange Syndrome
Inheritance: Autosomal Dominant, X-linked
Genes: NIPBL, RAD21, SMC3, HDAC8, SMC1A
Cornelia De Lange Syndrome: Features
Major features:
●Growth retardation
●Hirsuitism
●Severe-to-profound intellectual disability and developmental delay
●Limb reduction defects
●Craniofacial abnormalities
●Autistic/self-destructive behaviors
●Seizures
●Sensorineural hearing loss
●GERD
●Cryptorchidism
●Ptosis, nystagmus, myopia
●Congenital heart defects
●Vesicoureteral reflux
●Dysmorphic features:
oMicrobrachycephaly
oSynopphrys
oHighly arched eyebrows
oLong eyelashes
oLow-set, posteriorly rotated ears with thick helices
oDepressed/wide nasal bridge
oLong philtrum
oHigh-arched/cleft palate
oMicrognathia
oShort neck
●Mild CDLS exists
oMany of the same dysmorphic features
oLess severe intellectual disability and limb defectsDiamond-Blackfan Anemia
Inheritance: Autosomal dominant, X-linked
Genes: GATA1, RPLs and RPSs, TSR2
Diamond-Blackfan Anemia: Features
Major features:
●Normocytic or macrocytic anemia with normal platelets and leukocytes
●Increased risk for hematological malignancies and osteogenic sarcoma
●50% are dysmorphic
oKlippel-Feil anomaly
oUpper limb and hand deformities
●Genitourinary abnormalities
●CHDs
●Growth delayHypohidrotic Ectodermal Dysplasia (HED): Genetics
Inheritance: X-linked recessive, (less common: AD, AR)
Genes: EDA, EDAR (AD or AR), EDARADD (AR)
Hypohidrotic Ectodermal Dysplasia (HED) Major features
Major features:
●Most common form of ectodermal dysplasia
●Hypohidrosis (reduced ability to sweat)
oHyperthermia secondary to hypohidrosis
●Hypotrichosis
oLight-colored hair
●Hypodontia
●Small, pointed teeth/malformed teeth
●Frontal bossing
●Flattened nasal bridge
●Eczema
●Ozena (smelly discharge from the nose :/ )Incontinentia Pigmenti (IP): Genetics
Inheritance: X-linked dominant
Genes: IKBKG
Incontinentia Pigmenti (IP): Major features
Major features: ●4 stages oSkin blistering (birth – 4months) oWart-like rash (several months) oSwirling macular hyperpigmentation (6 months – adulthood) oLinear hypopogmentation ●Alopecia ●Hypodontia ●Dystrophic nails ●Cognitive delays ●Intellectual disability or learning disability
L1 Syndrome (X-Linked Hydrocephalus, MASA Syndrome, SPG1): Genetics
Inheritance: X-linked recessive
Genes: L1CAM
X-Linked Hydrocephalus Major features:
X-Linked Hydrocephalus Major features: ●Severe, prental-onset hydrocephalus ●Severe intellectual disability ●Adducted (clasped) thumbs ●Spasticity/brisk reflexes ●Stenosis of the aqueduct of Sylvius
MASA Syndrome Major Features: ● Mild-to-moderate intellectual disability (Mental retardation) ●Aphasia ●Spastic paraplegia ●Adducted thumbs ●Brain MRI abnormalities
SPG1 Major Features (X-linked complicated hereditary spastic paraplegia 1):
●Mild-to-moderate intellectual disability
●Spastic paraplegia
●Normal MRI
Rett Syndrome
Inheritance: X-linked dominant
Gene: MECP2
Major features: ●Typically male lethal ●Normal development followed by psychomotor regression beinning around age 2, which eventually plateaus ●Partial or complete loss of purposeful hand skills ●Partial or complete loss of spoken language ●Impaired or absent walking ability ●Hand stereotypies ●Severe intellectual disability ●Scoliosis ●Growth retardation ●Small, cold hands and feet ●Sleep disturbances ●Diminished pain response ●Communicate with eyes
Septo-Optic Dysplasia (de Morsier syndrome)
Inheritance: Multifactorial, Autosomal recessive, autosomal dominant
Genes: (RARELY DUE TO SINGLE GENE) HESX1
Septo-Optic Dysplasia (de Morsier syndrome) Major features
Major features:
●Optic nerve hypoplasia
oNystagmus
oPoor vision
●Pituitary hypoplasia/dysfunction
oGrowth hormone deficiency
oAbsence of hormone production (severe cases)
●Midline brain anomalies
oAbsence or underdevelopment of the cavum septum pellucidum (CSP)
oAbsence or underdevelopment of the corpus callosum
1/3 of patients with SOD have all three major features
