IllnessMacrosomia, congenital; differential diagnosis

NGS +

[Sanger]

Macrosomia refers to newborns at regular term carrying excessive birth weight (>4kg). The abnormal growth is the result of a disturbed interplay of genetic, epigenetic and hormonal factors that control human growth. Macrosomia is diagnosed after birth, often in the setting of poorly controlled gestational or pregestational diabetes; polyhydramnios are also common. Less commonly, overgrowth syndromes are observed such as Beckwith-Wiedemann (BWS), Simpson-Golabi-Behmel, Sotos, Weaver, Perlman, Tatton-Brown-Rahman, Parkes Weber, PTEN, PIK3CA syndromes or segmental overgrowth as in Proteus syndrome and others. Overgrowth syndromes are usually associated with health problems and in some cases carry increased risks for tumor development susceptibility and/or hormonal alterations, life-threatening hypoglycemia (e.g. BWS), seizures (Sotos syndrome) and developmental delay. The inheritance pattern of several of the above syndromes is autosomal dominant, but all other inheritance patterns occur, including epigenetic alterations and uniparental disomy (especially in BWS). The molecular genetic diagnostic yield in macrosomia is up to 80%, such as in the differential diagnosis of BWS. Thus, a negative result does not exclude the obvious clinical diagnosis.

References: doi: 10.3389/fped.2020.574857

https://www.ncbi.nlm.nih.gov/books/NBK1394/

https://www.ncbi.nlm.nih.gov/books/NBK1219/

https://www.ncbi.nlm.nih.gov/books/NBK1479/

https://www.ncbi.nlm.nih.gov/books/NBK153722/

• Alias: Genetic overgrowth/obesity syndrome
• Alias: Macrosomia adiposa congenita
• Allelic: Acute myeloid leukemia, somatic (DNMT3A)
• Allelic: Autism, susceptibility to, 18 (CHD8)
• Allelic: Basal ganglia calcification, idiopathic, 4 (PDGFRB)
• Allelic: Bladder cancer, somatic (HRAS)
• Allelic: Breast cancer, somatic (AKT1)
• Allelic: Breast cancer, somatic (PIK3CA)
• Allelic: Colorectal cancer, somatic (AKT1)
• Allelic: Colorectal cancer, somatic (PIK3CA)
• Allelic: Congenital myopathy with excess of muscle spindles (HRAS)
• Allelic: Cortical dysplasia, complex, with other brain malformations 10 (APC2)
• Allelic: Costello syndrome (HRAS)
• Allelic: Cowden syndrome 5 (PIK3CA)
• Allelic: Diabetes mellitus, type II (AKT2)
• Allelic: Focal cortical dysplasia, type II, somatic (MTOR)
• Allelic: Gastric cancer, somatic (PIK3CA)
• Allelic: Glioma susceptibility 2 (PTEN)
• Allelic: Hepatocellular carcinoma, somatic (PIK3CA)
• Allelic: Heyn-Sproul-Jackson syndrome (DNMT3A)
• Allelic: IMAGE syndrome (CGKN1C)
• Allelic: Joubert syndrome 10 (OFD1)
• Allelic: Keratosis, seborrheic, somatic (PIK3CA)
• Allelic: Macrodactyly, somatic (PIK3CA)
• Allelic: Marshall-Smith syndrome (NFIX)
• Allelic: Meningioma (PTEN)
• Allelic: Myeloproliferative disorder with eosinophilia (PDGFRB)
• Allelic: Myofibromatosis, infantile, 1 (PDGFRB)
• Allelic: Nevus sebaceous or woolly hair nevus, somatic (HRAS)
• Allelic: Nevus, epidermal, somatic (PIK3CA)
• Allelic: Nonsmall cell lung cancer, somatic (PIK3CA)
• Allelic: Orofaciodigital syndrome I (OFD1)
• Allelic: Ovarian cancer, somatic (AKT1)
• Allelic: Ovarian cancer, somatic (PIK3CA)
• Allelic: Premature aging syndrome, Penttinen type (PDGFRB)
• Allelic: Prostate cancer, somatic (PTEN)
• Allelic: Retinitis pigmentosa 23 (OFD1)
• Allelic: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic (HRAS)
• Allelic: Spitz nevus or nevus spilus, somatic (HRAS)
• Allelic: Thyroid carcinoma, follicular, somatic (HRAS)
• Allelic: Wilms tumor, somatic (GPC3)
• Beckwith-Wiedemann syndrome (CDKN1C)
• Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 [MONDO:0016475] (NLRP2)
• CLAPO syndrome, somatic (PIK3CA)
• CLOVE syndrome, somatic (PIK3CA)
• Capillary malformation-arteriovenous malformation 1 (RASA1)
• Cohen-Gibson syndrome (EED)
• Cowden syndrome 1 (PTEN)
• Cowden syndrome 6 (AKT1)
• Ehlers-Danlos syndrome, kyphoscoliotic type, 1 (PLOD1)
• Hypoinsulinemic hypoglycemia with hemihypertrophy (AKT2)
• Imagawa-Matsumoto syndrome (SUZ12)
• Keipert syndrome (GPC4)
• Kosaki overgrowth syndrome (PDGFRB)
• Lhermitte-Duclos syndrome (PTEN)
• Luscan-Lumish syndrome (SETD2)
• Macrocephaly, acquired, with impaired intellectual development (NFIB)
• Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, persistent fetal Hb (ZBTB7A)
• Macrocephaly/autism syndrome (PTEN)
• Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic (PIK3CA)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (PIK3R2)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (AKT3)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (CCND2)
• Mental retardation, XL 93 (BRWD3)
• Perlman syndrome (DIS3L2)
• Preimplantation embryonic lethality 2 (PADI6)
• Proteus syndrome, somatic (AKT1)
• Rahman syndrome (HIST1H1E)
• Shashi-Pena syndrome (ASXL2)
• Simpson-Golabi-Behmel syndrome, type 1 (GPC3)
• Simpson-Golabi-Behmel syndrome, type 2 (OFD1)
• Smith-Kingsmore syndrome (MTOR)
• Sotos syndrome 1 (NSD1)
• Sotos syndrome 2 (NFIX)
• Tatton-Brown-Rahman syndrome (DNMT3A)
• Tenorio syndrome (RNF125)
• Weaver syndrome (EZH2)