Table 3.

Disorders to Consider in the Differential Diagnosis of Simpson-Golabi-Behmel Syndrome Type 1

Gene(s)DisorderMOIClinical Features of This Disorder
Overlapping w/SGBS1Distinguishing from SGBS1
See footnote 1.Beckwith-Wiedemann syndrome (BWS)See footnote 1.
  • Macrosomia
  • Macroglossia
  • Ear anomalies
  • Diastasis recti
  • Hypoglycemia
  • Genitourinary malformations
  • ↑ incidence of tumors
  • Appreciably different facial features (midface flattening in BWS; broader forehead in SGBS1)
  • Absence of relative macrocephaly
  • Absence of skeletal abnormalities
  • Omphalocele
  • Phenotype often less pronounced w/age (In SGBS1, characteristic features may not be present in infancy.)
  • Hemihypertrophy/lateralized overgrowth more common
  • Persons w/BWS are less tall & less dysmorphic, w/fewer visceral & skeletal malformations.
DIS3L2 Perlman syndrome (OMIM 267000)AR
  • Macrosomia
  • High incidence of Wilms tumor
  • Distinctive facial features
  • Neonatal mortality is high.
DNMT3A Tatton-Brown-Rahman syndrome (DNMT3A overgrowth syndrome)AD
  • Overgrowth
  • macrocephaly
  • Intellectual disability
  • Cryptorchidism
  • Behavioral/psychiatric issues
  • Seizures
  • Distinctive facial features
  • Acute myeloid leukemia predisposition
  • Joint hypermobility
  • Hypotonia
EZH2 EZH2-related Weaver syndrome (See EZH2-Related Overgrowth.)AD
  • Overgrowth
  • Umbilical hernia
  • Ear anomalies
  • Hypotonia
  • Advanced bone age
  • Vertebral defects
  • Hypertelorism
  • Flat occiput
  • Deep horizontal chin crease, large ears
  • Absence of downslanting palpebral fissures, dental malocclusion, & central groove of lower lip (all characteristic of SGBS1 2)
  • Psychomotor delay typically more prominent
NFIX NFIX-related Malan syndrome (OMIM 614753)AD
  • Postnatal overgrowth
  • Advanced bone age
  • Macrocephaly
  • Downslanting palpebral fissures
  • Marfanoid habitus w/long & slender body, low body mass, long & narrow face, arachnodactyly, long tapered fingers
  • Aggressive, self-injurious behavior
  • Normal birth weight
NFIX Marshall-Smith syndrome (OMIM 602535)AD
  • Advanced bone age
  • Intellectual disability
  • Distinctive facial features
  • Predisposition to fractures
NSD1 Sotos syndrome AD
  • Hypertelorism
  • Broad forehead
  • Downslanting palpebral fissures
  • Hypoglycemia
Seizures are more common. 2
OFD1
PIGA 3		Simpson-Golabi-Behmel syndrome type 2 (infantile-lethal form) (OMIM 300209)XL
  • Macrosomia
  • Widely spaced eyes, epicanthal folds, downslanted palpebral fissures
  • Redundant, furrowed skin over the glabella
  • Wide nasal bridge & anteverted nares in infants; broad nose & coarse facial appearance in older persons
  • Macrocephaly
  • Macrostomia
  • Macroglossia
  • Cleft lip &/or submucous cleft palate (w/bifid uvula); high & narrow palate
  • Small mandible (micrognathia) in neonates; macrognathia in older persons
  • Multiple congenital anomalies
More lethal form usually assoc w/hydrops fetalis 4
PIGN Fryns syndrome AR
  • Coarse facies
  • Diaphragmatic hernia w/lung hypoplasia
  • Cleft lip/palate
  • Congenital heart defects
  • Ear anomalies
  • Macrostomia
  • Hydrocephalus
  • Micro- & retrognathia
PLOD1 Nevo syndrome 5 (See PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome.)AR
  • Overgrowth
  • Vertebral anomalies
  • Ear malformations
  • Cryptorchidism
  • Intellectual disability
  • Accelerated osseous maturation
  • Large extremities
  • Hypotonia
PTCH Nevoid basal cell carcinoma syndrome (Gorlin syndrome)AD
  • Macrocephaly
  • Coarse facial features
  • Bifid ribs
  • Multiple jaw keratocysts frequently beginning in 2nd decade of life
  • Basal cell carcinomas usually from 3rd decade onward
SETD2 SETD2-related neurodevelopmental disorder w/macrocephaly/
overgrowth (also referred to as Luscan-Lumish syndrome or Sotos-like syndrome) (See SETD2 Neurodevelopmental Disorders.)		AD
  • Intellectual Disability
  • Macrocephaly
  • Overgrowth
  • Advanced bone age
  • Frontal bossing
  • Low-set ears
  • Behavioral findings
  • Eye findings
  • Hypotonia
  • Hyponatremia
  • Respiratory issues
  • Epilepsy
  • Arched eyebrows
  • Micrognathia w/mandibular hypoplasia
SUZ12 SUZ12-related overgrowth syndrome (Imagawa-Matsumoto syndrome) (OMIM 618786)AD
  • Pre- and postnatal overgrowth
  • Macrocephaly
  • Frontal bossing
  • Hypertelorism
  • Downslanting palpebral fissures
  • Low & broad nasal bridge
  • Musculoskeletal abnormalities
  • Genitourinary abnormalities (umbilical hernia, cryptorchidism)
  • Structural brain abnormalities
  • Respiratory issues, scoliosis
  • Widened distal ulnas
  • Widened distal femurs
  • Coxa valga
  • Flat feet
  • Pronation of feet
  • ↓ muscle bulk
  • Phimosis
  • Recurrent respiratory infections
  • Aspiration of thin liquids
1.

BWS is associated with abnormal regulation of gene transcription in two imprinted domains on chromosome 11p15.5 (also known as the BWS critical region). Regulation may be disrupted by any one of numerous mechanisms. Approximately 85% of individuals with BWS have no family history of BWS; approximately 15% have a family history consistent with parent-of-origin autosomal dominant transmission.

2.
3.
4.
5.

Giunta et al [2005] convincingly demonstrated that Nevo syndrome is part of the spectrum of kEDS; thus, the term "Nevo syndrome" does not refer to a distinct disorder but is now incorporated into kEDS.

From: Simpson-Golabi-Behmel Syndrome Type 1

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