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Progressive macrocephaly

MedGen UID:
395368
Concept ID:
C1859896
Finding
Synonyms: Macrocephaly, progressive; Progressively abnormally enlarging cranium; Progressively abnormally enlarging skull
 
HPO: HP:0004481

Definition

The progressive development of an abnormally large skull. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Progressive macrocephaly

Conditions with this feature

Alexander disease
MedGen UID:
78724
Concept ID:
C0270726
Disease or Syndrome
Alexander disease, a progressive disorder of cerebral white matter caused by a heterozygous GFAP pathogenic variant, comprises a continuous clinical spectrum most recognizable in infants and children and a range of nonspecific neurologic manifestations in adults. This chapter discusses the spectrum of Alexander disease as four forms: neonatal, infantile, juvenile, and adult. The neonatal form begins in the first 30 days after birth with neurologic findings (e.g., hypotonia, hyperexcitability, myoclonus) and/or gastrointestinal manifestations (e.g., gastroesophageal reflux, vomiting, failure to thrive), followed by severe developmental delay and regression, seizures, megalencephaly, and typically death within two years. The infantile form is characterized by variable developmental issues: initially some have delayed or plateauing of acquisition of new skills, followed in some by a loss of gross and fine motor skills and language during in the first decade or in others a slow disease course that spans decades. Seizures, often triggered by illness, may be less frequent/severe than in the neonatal form. The juvenile form typically presents in childhood or adolescence with clinical and imaging features that overlap with the other forms. Manifestations in early childhood are milder than those in the infantile form (e.g., mild language delay may be the only developmental abnormality or, with language acquisition, hypophonia or nasal speech may alter the voice, often prior to appearance of other neurologic features). Vomiting and failure to thrive as well as scoliosis and autonomic dysfunction are common. The adult form is typically characterized by bulbar or pseudobulbar findings (palatal myoclonus, dysphagia, dysphonia, dysarthria or slurred speech), motor/gait abnormalities with pyramidal tract signs (spasticity, hyperreflexia, positive Babinski sign), or cerebellar abnormalities (ataxia, nystagmus, or dysmetria). Others may have hemiparesis or hemiplegia with a relapsing/remitting course or slowly progressive quadriparesis or quadriplegia. Other neurologic features can include sleep apnea, diplopia or disorders of extraocular motility, and autonomic dysfunction.
Mitochondrial complex I deficiency
MedGen UID:
374101
Concept ID:
C1838979
Disease or Syndrome
Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome (see these terms).
Megalencephaly-capillary malformation-polymicrogyria syndrome
MedGen UID:
355421
Concept ID:
C1865285
Disease or Syndrome
PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia. Prior to the identification of PIK3CA as the causative gene, PROS was separated into distinct clinical syndromes based on the tissues and/or organs involved (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency.
PTEN hamartoma tumor syndrome with granular cell tumor
MedGen UID:
400984
Concept ID:
C1866376
Neoplastic Process
Cowden syndrome 5
MedGen UID:
767432
Concept ID:
C3554518
Disease or Syndrome
PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia. Prior to the identification of PIK3CA as the causative gene, PROS was separated into distinct clinical syndromes based on the tissues and/or organs involved (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency.
Cowden syndrome 6
MedGen UID:
767433
Concept ID:
C3554519
Disease or Syndrome
\n\nThe features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors.  Some people with Cowden syndrome have relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other affected individuals have the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome (named for the genetic cause of the conditions) instead of two distinct conditions.\n\nSome people do not meet the strict criteria for a clinical diagnosis of Cowden syndrome, but they have some of the characteristic features of the condition, particularly the cancers. These individuals are often described as having Cowden-like syndrome. Both Cowden syndrome and Cowden-like syndrome are caused by mutations in the same genes.\n\nCowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include kidney cancer, colorectal cancer, and an agressive form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. People with Cowden syndrome are also more likely to develop more than one cancer during their lifetimes compared to the general population. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development, intellectual disability, or autism spectrum disorder, which can affect communication and social interaction.\n\nAlmost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties.\n\nCowden syndrome is a genetic disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers.

Professional guidelines

PubMed

Mulugeta B, Seyoum G, Mekonnen A, Ketema E
BMC Pediatr 2022 Mar 18;22(1):145. doi: 10.1186/s12887-022-03212-6. PMID: 35303805Free PMC Article

Recent clinical studies

Etiology

Alshareef M, Tyler M, Litts C, Pearce J, Yazdani M, Eskandari R
World Neurosurg 2022 Aug;164:e973-e979. Epub 2022 May 27 doi: 10.1016/j.wneu.2022.05.079. PMID: 35636660
Mulugeta B, Seyoum G, Mekonnen A, Ketema E
BMC Pediatr 2022 Mar 18;22(1):145. doi: 10.1186/s12887-022-03212-6. PMID: 35303805Free PMC Article
Dewan MC, Lim J, Morgan CD, Gannon SR, Shannon CN, Wellons JC 3rd, Naftel RP
J Neurosurg Pediatr 2016 Dec;25(6):655-662. Epub 2016 Aug 26 doi: 10.3171/2016.6.PEDS1675. PMID: 27564786
Schulz M, Ahmadi SA, Spors B, Thomale UW
Acta Neurochir Suppl 2012;114:261-6. doi: 10.1007/978-3-7091-0956-4_51. PMID: 22327705
Conti S, Condò M, Posar A, Mari F, Resta N, Renieri A, Neri I, Patrizi A, Parmeggiani A
J Child Neurol 2012 Mar;27(3):392-7. Epub 2011 Sep 29 doi: 10.1177/0883073811420296. PMID: 21960672

Diagnosis

Habib MH, Alavi MZ, Goraya A, Zaman S, Ahmed A
J Med Case Rep 2022 Nov 4;16(1):427. doi: 10.1186/s13256-022-03615-0. PMID: 36333774Free PMC Article
Alshareef M, Tyler M, Litts C, Pearce J, Yazdani M, Eskandari R
World Neurosurg 2022 Aug;164:e973-e979. Epub 2022 May 27 doi: 10.1016/j.wneu.2022.05.079. PMID: 35636660
Mulugeta B, Seyoum G, Mekonnen A, Ketema E
BMC Pediatr 2022 Mar 18;22(1):145. doi: 10.1186/s12887-022-03212-6. PMID: 35303805Free PMC Article
Kahle KT, Kulkarni AV, Limbrick DD Jr, Warf BC
Lancet 2016 Feb 20;387(10020):788-99. Epub 2015 Aug 6 doi: 10.1016/S0140-6736(15)60694-8. PMID: 26256071
Hanssen AM, Fryns JP
J Med Genet 1995 Feb;32(2):117-9. doi: 10.1136/jmg.32.2.117. PMID: 7760320Free PMC Article

Therapy

Visagan R, Livermore LJ, Kelly D, Magdum S
BMJ Case Rep 2017 Oct 11;2017 doi: 10.1136/bcr-2017-221849. PMID: 29025781Free PMC Article
Dewan MC, Lim J, Morgan CD, Gannon SR, Shannon CN, Wellons JC 3rd, Naftel RP
J Neurosurg Pediatr 2016 Dec;25(6):655-662. Epub 2016 Aug 26 doi: 10.3171/2016.6.PEDS1675. PMID: 27564786
Sufianov AA, Gaibov SS, Sufianov RA
J Neurosurg Pediatr 2015 Jul;16(1):107-11. Epub 2015 Apr 24 doi: 10.3171/2014.12.PEDS14306. PMID: 25910036

Prognosis

Habib MH, Alavi MZ, Goraya A, Zaman S, Ahmed A
J Med Case Rep 2022 Nov 4;16(1):427. doi: 10.1186/s13256-022-03615-0. PMID: 36333774Free PMC Article
Visagan R, Livermore LJ, Kelly D, Magdum S
BMJ Case Rep 2017 Oct 11;2017 doi: 10.1136/bcr-2017-221849. PMID: 29025781Free PMC Article
Dewan MC, Lim J, Morgan CD, Gannon SR, Shannon CN, Wellons JC 3rd, Naftel RP
J Neurosurg Pediatr 2016 Dec;25(6):655-662. Epub 2016 Aug 26 doi: 10.3171/2016.6.PEDS1675. PMID: 27564786
Roth J, Ben-Sira L, Udayakumaran S, Constantini S
Childs Nerv Syst 2012 Mar;28(3):453-9. Epub 2011 Nov 29 doi: 10.1007/s00381-011-1639-y. PMID: 22124573
Blumberg DL, Sklar CA, David R, Rothenberg S, Bell J
Pediatrics 1989 Jun;83(6):998-1002. PMID: 2657629

Clinical prediction guides

Ries M, Mendoza G, Arash-Kaps L, Amraoui Y, Quack F, Hardt B, Diederich S, Beck M, Mengel E
Genet Med 2022 Dec;24(12):2434-2443. Epub 2022 Oct 4 doi: 10.1016/j.gim.2022.09.001. PMID: 36194207
Dewan MC, Lim J, Morgan CD, Gannon SR, Shannon CN, Wellons JC 3rd, Naftel RP
J Neurosurg Pediatr 2016 Dec;25(6):655-662. Epub 2016 Aug 26 doi: 10.3171/2016.6.PEDS1675. PMID: 27564786
Harada A, Miya F, Utsunomiya H, Kato M, Yamanaka T, Tsunoda T, Kosaki K, Kanemura Y, Yamasaki M
Childs Nerv Syst 2015 Mar;31(3):465-71. Epub 2014 Nov 22 doi: 10.1007/s00381-014-2589-y. PMID: 25416470
Schulz M, Ahmadi SA, Spors B, Thomale UW
Acta Neurochir Suppl 2012;114:261-6. doi: 10.1007/978-3-7091-0956-4_51. PMID: 22327705

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