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Neurodevelopmental disorder with microcephaly, short stature, and speech delay(NEDMISS)

MedGen UID:
1823984
Concept ID:
C5774211
Disease or Syndrome
Synonym: NEDMISS
 
Gene (location): TRAPPC10 (21q22.3)
 
Monarch Initiative: MONDO:0859285
OMIM®: 620027

Definition

Neurodevelopmental disorder with microcephaly, short stature, and speech delay (NEDMISS) is an autosomal recessive disorder characterized by global developmental delay with severely impaired intellectual development usually accompanied by behavioral abnormalities. Other features may include hypotonia, abnormal gait, mild dysmorphism, and seizures (Rawlins et al., 2022). [from OMIM]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
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.
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.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.

Recent clinical studies

Diagnosis

Corona-Rivera JR, Martínez-Duncker I, Morava E, Ranatunga W, Salinas-Marin R, González-Jaimes AM, Castillo-Reyes KA, Peña-Padilla C, Bobadilla-Morales L, Corona-Rivera A, Orozco-Vela M, Brukman-Jiménez SA
Mol Genet Metab 2024 May;142(1):108469. Epub 2024 Mar 28 doi: 10.1016/j.ymgme.2024.108469. PMID: 38564972
Hüffmeier U, Kraus C, Reuter MS, Uebe S, Abbott MA, Ahmed SA, Rawson KL, Barr E, Li H, Bruel AL, Faivre L, Tran Mau-Them F, Botti C, Brooks S, Burns K, Ward DI, Dutra-Clarke M, Martinez-Agosto JA, Lee H, Nelson SF; UCLA California Center for Rare Disease, Zacher P, Abou Jamra R, Klöckner C, McGaughran J, Kohlhase J, Schuhmann S, Moran E, Pappas J, Raas-Rothschild A, Sacoto MJG, Henderson LB, Palculict TB, Mullegama SV, Zghal Elloumi H, Reich A, Schrier Vergano SA, Wahl E, Reis A, Zweier C
Orphanet J Rare Dis 2021 Mar 18;16(1):136. doi: 10.1186/s13023-021-01744-1. PMID: 33736665Free PMC Article
Lévy J, Coussement A, Dupont C, Guimiot F, Baumann C, Viot G, Passemard S, Capri Y, Drunat S, Verloes A, Pipiras E, Benzacken B, Dupont JM, Tabet AC
Am J Med Genet A 2017 Aug;173(8):2081-2087. Epub 2017 Jun 1 doi: 10.1002/ajmg.a.38302. PMID: 28573701
van Bon BW, Koolen DA, Brueton L, McMullan D, Lichtenbelt KD, Adès LC, Peters G, Gibson K, Moloney S, Novara F, Pramparo T, Dalla Bernardina B, Zoccante L, Balottin U, Piazza F, Pecile V, Gasparini P, Guerci V, Kets M, Pfundt R, de Brouwer AP, Veltman JA, de Leeuw N, Wilson M, Antony J, Reitano S, Luciano D, Fichera M, Romano C, Brunner HG, Zuffardi O, de Vries BB
Eur J Hum Genet 2010 Feb;18(2):163-70. Epub 2009 Oct 7 doi: 10.1038/ejhg.2009.152. PMID: 19809484Free PMC Article
Zackai EH, Mellman WJ, Neiderer B, Hanson JW
J Pediatr 1975 Aug;87(2):280-4. doi: 10.1016/s0022-3476(75)80603-2. PMID: 50427

Therapy

Wu W, Chen R
Mol Genet Genomic Med 2023 Jan;11(1):e2066. Epub 2022 Sep 24 doi: 10.1002/mgg3.2066. PMID: 36153657Free PMC Article
Özer E, Karaman B, Güneş N, Evliyaoğlu O, Tüysüz B
Turk J Pediatr 2021;63(1):174-180. doi: 10.24953/turkjped.2021.01.022. PMID: 33686842
Zackai EH, Mellman WJ, Neiderer B, Hanson JW
J Pediatr 1975 Aug;87(2):280-4. doi: 10.1016/s0022-3476(75)80603-2. PMID: 50427

Prognosis

Pauly M, Krumbiegel M, Trumpp S, Braig S, Rupprecht T, Kraus C, Uebe S, Reis A, Vasileiou G
Clin Genet 2024 Aug;106(2):180-186. Epub 2024 Apr 11 doi: 10.1111/cge.14532. PMID: 38604781
Lévy J, Coussement A, Dupont C, Guimiot F, Baumann C, Viot G, Passemard S, Capri Y, Drunat S, Verloes A, Pipiras E, Benzacken B, Dupont JM, Tabet AC
Am J Med Genet A 2017 Aug;173(8):2081-2087. Epub 2017 Jun 1 doi: 10.1002/ajmg.a.38302. PMID: 28573701

Clinical prediction guides

Pauly M, Krumbiegel M, Trumpp S, Braig S, Rupprecht T, Kraus C, Uebe S, Reis A, Vasileiou G
Clin Genet 2024 Aug;106(2):180-186. Epub 2024 Apr 11 doi: 10.1111/cge.14532. PMID: 38604781
Hüffmeier U, Kraus C, Reuter MS, Uebe S, Abbott MA, Ahmed SA, Rawson KL, Barr E, Li H, Bruel AL, Faivre L, Tran Mau-Them F, Botti C, Brooks S, Burns K, Ward DI, Dutra-Clarke M, Martinez-Agosto JA, Lee H, Nelson SF; UCLA California Center for Rare Disease, Zacher P, Abou Jamra R, Klöckner C, McGaughran J, Kohlhase J, Schuhmann S, Moran E, Pappas J, Raas-Rothschild A, Sacoto MJG, Henderson LB, Palculict TB, Mullegama SV, Zghal Elloumi H, Reich A, Schrier Vergano SA, Wahl E, Reis A, Zweier C
Orphanet J Rare Dis 2021 Mar 18;16(1):136. doi: 10.1186/s13023-021-01744-1. PMID: 33736665Free PMC Article
Özer E, Karaman B, Güneş N, Evliyaoğlu O, Tüysüz B
Turk J Pediatr 2021;63(1):174-180. doi: 10.24953/turkjped.2021.01.022. PMID: 33686842
Jiang M, Wang S, Li F, Geng J, Ji Y, Li K, Jiang X
Medicine (Baltimore) 2020 Nov 6;99(45):e23033. doi: 10.1097/MD.0000000000023033. PMID: 33157955Free PMC Article

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