U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Macrocephaly-developmental delay syndrome(MRT41)

MedGen UID:
816555
Concept ID:
C3810225
Mental or Behavioral Dysfunction
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 41; MRT41
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): KPTN (19q13.32)
 
Monarch Initiative: MONDO:0014289
OMIM®: 615637
Orphanet: ORPHA397612

Disease characteristics

Excerpted from the GeneReview: KPTN-Related Disorder
KPTN-related disorder is characterized by mild-to-profound intellectual disability, global developmental delay, neurobehavioral/psychiatric manifestations (anxiety, stereotypies, hyperactivity, repetitive speech, and impaired social communication), hypotonia, postnatal and progressive macrocephaly, and seizures. Generalized megalencephaly is often present on brain imaging. Some individuals have recurrent infections, conductive hearing impairment, strabismus, nystagmus, ketotic hypoglycemia, thyroid dysfunction, and/or mild skeletal manifestations. [from GeneReviews]
Authors:
Lettie E Rawlins  |  Peter B Crino  |  Philip H Iffland, et. al.   view full author information

Additional description

From OMIM
Autosomal recessive intellectual developmental disorder-41 (MRT41) is characterized by macrocephaly and global developmental delay. Some patients have seizures (Baple et al., 2014).  http://www.omim.org/entry/615637

Clinical features

From HPO
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Isolated scaphocephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Prominent fingertip pads
MedGen UID:
322758
Concept ID:
C1835807
Finding
A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMacrocephaly-developmental delay syndrome
Follow this link to review classifications for Macrocephaly-developmental delay syndrome in Orphanet.

Professional guidelines

PubMed

Nierenberg AA, Agustini B, Köhler-Forsberg O, Cusin C, Katz D, Sylvia LG, Peters A, Berk M
JAMA 2023 Oct 10;330(14):1370-1380. doi: 10.1001/jama.2023.18588. PMID: 37815563
Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE; International PCOS Network
Eur J Endocrinol 2023 Aug 2;189(2):G43-G64. doi: 10.1093/ejendo/lvad096. PMID: 37580861
Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE
J Clin Endocrinol Metab 2023 Sep 18;108(10):2447-2469. doi: 10.1210/clinem/dgad463. PMID: 37580314Free PMC Article

Recent clinical studies

Etiology

Tavares J, Reizinho C, Luís A
BMJ Case Rep 2025 Jan 19;18(1) doi: 10.1136/bcr-2024-263801. PMID: 39828312
Sorber R, Hicks CW
Curr Cardiol Rep 2022 Mar;24(3):209-216. Epub 2022 Jan 14 doi: 10.1007/s11886-022-01642-3. PMID: 35029783Free PMC Article
Vilacosta I, San Román JA, di Bartolomeo R, Eagle K, Estrera AL, Ferrera C, Kaji S, Nienaber CA, Riambau V, Schäfers HJ, Serrano FJ, Song JK, Maroto L
J Am Coll Cardiol 2021 Nov 23;78(21):2106-2125. doi: 10.1016/j.jacc.2021.09.022. PMID: 34794692
Camilleri M, Chedid V, Ford AC, Haruma K, Horowitz M, Jones KL, Low PA, Park SY, Parkman HP, Stanghellini V
Nat Rev Dis Primers 2018 Nov 1;4(1):41. doi: 10.1038/s41572-018-0038-z. PMID: 30385743
Strayer RJ
Emerg Med Clin North Am 2017 Nov;35(4):713-725. doi: 10.1016/j.emc.2017.06.002. PMID: 28987425

Diagnosis

Yates T
Handb Clin Neurol 2023;198:241-247. doi: 10.1016/B978-0-12-823356-6.00013-5. PMID: 38043967
Sorber R, Hicks CW
Curr Cardiol Rep 2022 Mar;24(3):209-216. Epub 2022 Jan 14 doi: 10.1007/s11886-022-01642-3. PMID: 35029783Free PMC Article
Morello F, Santoro M, Fargion AT, Grifoni S, Nazerian P
Intern Emerg Med 2021 Jan;16(1):171-181. Epub 2020 May 1 doi: 10.1007/s11739-020-02354-8. PMID: 32358680
Mulroy E, Balint B, Bhatia KP
Pract Neurol 2020 Oct;20(5):368-376. Epub 2020 Jun 2 doi: 10.1136/practneurol-2020-002566. PMID: 32487722
Strayer RJ
Emerg Med Clin North Am 2017 Nov;35(4):713-725. doi: 10.1016/j.emc.2017.06.002. PMID: 28987425

Therapy

Tavares J, Reizinho C, Luís A
BMJ Case Rep 2025 Jan 19;18(1) doi: 10.1136/bcr-2024-263801. PMID: 39828312
Calvani M, Anania C, Bianchi A, D'Auria E, Cardinale F, Votto M, Martelli A, Tosca M, Chiappini E, Brambilla I, Miraglia Del Giudice M, Caffarelli C
Acta Biomed 2021 Nov 29;92(S7):e2021518. doi: 10.23750/abm.v92iS7.12394. PMID: 34842596Free PMC Article
Mulroy E, Balint B, Bhatia KP
Pract Neurol 2020 Oct;20(5):368-376. Epub 2020 Jun 2 doi: 10.1136/practneurol-2020-002566. PMID: 32487722
Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, Tan J, Liang X, Cao Y, Wang Z, Qin Y, Zhao H, Zhou Y, Ren H, Hao G, Ling X, Zhao J, Zhang Y, Qi X, Zhang L, Deng X, Chen X, Zhu Y, Wang X, Tian LF, Lv Q, Ma X, Zhang H, Legro RS, Chen ZJ
Lancet 2019 Mar 30;393(10178):1310-1318. Epub 2019 Feb 28 doi: 10.1016/S0140-6736(18)32843-5. PMID: 30827784
Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, Fruhwald S, Hiesmayr M, Ichai C, Jakob SM, Loudet CI, Malbrain ML, Montejo González JC, Paugam-Burtz C, Poeze M, Preiser JC, Singer P, van Zanten AR, De Waele J, Wendon J, Wernerman J, Whitehouse T, Wilmer A, Oudemans-van Straaten HM; ESICM Working Group on Gastrointestinal Function
Intensive Care Med 2017 Mar;43(3):380-398. Epub 2017 Feb 6 doi: 10.1007/s00134-016-4665-0. PMID: 28168570Free PMC Article

Prognosis

Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Karol LA
J Pediatr Orthop 2019 Jul;39(Issue 6, Supplement 1 Suppl 1):S38-S43. doi: 10.1097/BPO.0000000000001351. PMID: 31169646
Brownlee WJ, Miller DH
J Clin Neurosci 2014 Dec;21(12):2065-71. Epub 2014 Jul 11 doi: 10.1016/j.jocn.2014.02.026. PMID: 25027666
O'Leary PF, Shanahan F
Curr Gastroenterol Rep 2002 Oct;4(5):373-82. doi: 10.1007/s11894-002-0007-1. PMID: 12228039
Gill SS, Heuman DM, Mihas AA
J Clin Gastroenterol 2001 Oct;33(4):267-82. doi: 10.1097/00004836-200110000-00004. PMID: 11588539

Clinical prediction guides

Story CM, Gerber GF, Chaturvedi S
Hematology Am Soc Hematol Educ Program 2023 Dec 8;2023(1):745-753. doi: 10.1182/hematology.2023000501. PMID: 38066937Free PMC Article
Sanchez-Jimeno C, Blanco-Kelly F, López-Grondona F, Losada-Del Pozo R, Moreno B, Rodrigo-Moreno M, Martinez-Cayuelas E, Riveiro-Alvarez R, Fenollar-Cortés M, Ayuso C, Rodríguez de Alba M, Lorda-Sanchez I, Almoguera B
Genes (Basel) 2021 Aug 30;12(9) doi: 10.3390/genes12091360. PMID: 34573342Free PMC Article
Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Brownlee WJ, Miller DH
J Clin Neurosci 2014 Dec;21(12):2065-71. Epub 2014 Jul 11 doi: 10.1016/j.jocn.2014.02.026. PMID: 25027666
Strehle EM, Bantock HM
Genet Couns 2003;14(2):195-205. PMID: 12872814

Recent systematic reviews

González-Rubino JB, Vinolo-Gil MJ, Martín-Valero R
Support Care Cancer 2023 Apr 12;31(5):257. doi: 10.1007/s00520-023-07666-x. PMID: 37043039Free PMC Article
Gil Martínez V, Avedillo Salas A, Santander Ballestín S
Nutrients 2022 Feb 28;14(5) doi: 10.3390/nu14051033. PMID: 35268010Free PMC Article
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Payne LE, Gagnon DJ, Riker RR, Seder DB, Glisic EK, Morris JG, Fraser GL
Crit Care 2017 Nov 14;21(1):276. doi: 10.1186/s13054-017-1856-1. PMID: 29137682Free PMC Article
van Sleuwen BE, Engelberts AC, Boere-Boonekamp MM, Kuis W, Schulpen TW, L'Hoir MP
Pediatrics 2007 Oct;120(4):e1097-106. doi: 10.1542/peds.2006-2083. PMID: 17908730

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...